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1. Potent human broadly SARS-CoV-2–neutralizing IgA and IgG antibodies effective against Omicron BA.1 and BA.2

Author: Planchais, Cyril, Fernández, Ignacio, Bruel, Timothée, de Melo, Guilherme, Prot, Matthieu, Beretta, Maxime, Guardado-Calvo, Pablo, Dufloo, Jérémy, Molinos-Albert, Luis, Backovic, Marija, Chiaravalli, Jeanne, Giraud, Emilie, Vesin, Benjamin, Conquet, Laurine, Grzelak, Ludivine, Planas, Delphine, Staropoli, Isabelle, Guivel-Benhassine, Florence, Hieu, Thierry, Boullé, Mikaël, Cervantes-Gonzalez, Minerva, Ungeheuer, Marie-Noëlle, Charneau, Pierre, van der Werf, Sylvie, Agou, Fabrice, Bartoli, Marie, Diallo, Alpha, Le Mestre, Soizic, Paul, Christelle, Petrov-Sanchez, Ventzislava, Yazdanpanah, Yazdan, Ficko, Cécile, Chirouze, Catherine, Andrejak, Claire, Malvy, Denis, Goehringer, François, Rossignol, Patrick, Gigante, Tristan, Gilg, Morgane, Rossignol, Bénédicte, Etienne, Manuel, Beluze, Marine, Bachelet, Delphine, Bhavsar, Krishna, Bouadma, Lila, Chair, Anissa, Charpentier, Charlotte, Chenard, Léo, Couffignal, Camille, Debray, Marie-Pierre, Descamps, Diane, Duval, Xavier, Eloy, Philippine, Esposito-Farese, Marina, Florence, Aline-Marie, Ghosn, Jade, Hoffmann, Isabelle, Kafif, Ouifiya, Khalil, Antoine, Lafhej, Nadhem, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Hingrat, Quentin, Letrou, Sophie, Mentré, France, Peytavin, Gilles, Piquard, Valentine, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Timsit, Jean-François, Tubiana, Sarah, Visseaux, Benoît, Deplanque, Dominique, Hulot, Jean-Sébastien, Diehl, Jean-Luc, Picone, Olivier, Angoulvant, François, Abrous, Amal, Couffin-Cadiergues, Sandrine, da Silva, Fernanda, Esperou, Hélène, Houas, Ikram, Jaafoura, Salma, Papadopoulos, Aurélie, Gaymard, Alexandre, Lina, Bruno, Rosa-Calatrava, Manuel, Dorival, Céline, Guedj, Jérémie, Lingas, Guillaume, Neant, Nadège, Abel, Laurent, Manda, Victoria, Behillil, Sylvie, Enouf, Vincent, Levy, Yves, Wiedemann, Aurélie, Arowas, Laurence, Perlaza, Blanca, Perrin de Facci, Louise, Chaouche, Sophie, Sangari, Linda, Renaudat, Charlotte, Fernandes Pellerin, Sandrine, van Platen, Cassandre, Jolly, Nathalie, Kuhmel, Lucie, Garaud, Valentine, Rafanoson, Hantaniaina, Gardais, Soazic, de Parseval, Nathalie, Dugast, Claire, Jannet, Caroline, Ropars, Sandrine, Momboisse, Fanny, Porteret, Isabelle, Cailleau, Isabelle, Hoen, Bruno, Tondeur, Laura, Besombes, Camille, Fontanet, Arnaud, Dimitrov, Jordan, Simon-Lorière, Etienne, Bourhy, Hervé, Montagutelli, Xavier, Rey, Félix, Schwartz, Olivier, Mouquet, Hugo, Covid Cohort Study Group, French, Study Group, Corser, Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Criblage chémogénomique et biologique (Plateforme) - Chemogenomic and Biological Screening Platform (PF-CCB), Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris] (IP)-TheraVectys-Université Paris Cité (UPCité), Génétique de la souris - Mouse Genetics, Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), FundingFunder(s): Institut PasteurFunder(s): French Government’s Investissements d’Avenir program Award Id(s): ANR-11-EQPX-0008Funder(s): Institut national de la santé et de la recherche médicaleFunder(s): REsearch & ACtion emergING infectious diseases (REACTing) consortiumFunder(s): Ministry of Health and Social AffairsFunder(s): Ministry of Higher Education and ResearchFunder(s): Agence Nationale de la Recherche Award Id(s): #20RR028-00Funder(s): European Commission Award Id(s): #101003589Funder(s): Fondation de France Award Id(s): #00106077Funder(s): Agence Nationale de Recherches sur le Sida et les Hépatites ViralesFunder(s): Programme hospitalier de recherche clinique Award Id(s): 20-0424, ANR-11-EQPX-0008,CACSICE,Centre d'analyse de systèmes complexes dans les environnements complexes(2011), ANR-21-CO14-0007,CoronaMito,Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale(2021), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Virologie Structurale, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Processus infectieux à Trypanosomatidés - Trypanosomatids Infectious Processes, Institut Pasteur [Paris]-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Interactions Virus-Insectes - Insect-Virus Interactions (IVI), and Institut Pasteur [Paris]-TheraVectys-Université Paris Cité (UPCité)
Subjects: [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, SARS-CoV-2, Immunoglobulin G, Spike Glycoprotein, Coronavirus, Immunology, Animals, COVID-19, Humans, Immunology and Allergy, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Antibodies, Viral, Antibodies, Neutralizing, Immunoglobulin A
Abstract: International audience; Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute to long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide SARS-CoV-2 immunoprofiling in Wuhan COVID-19 convalescents combining serological, cellular, and monoclonal antibody explorations revealed humoral immunity coordination. Detailed characterization of a hundred SARS-CoV-2 spike memory B-cell monoclonal antibodies uncovered diversity in their repertoire and antiviral functions. The latter were influenced by the targeted spike region with strong Fc-dependent effectors to the S2 subunit and potent neutralizers to the receptor-binding domain. Amongst those, Cv2.1169 and Cv2.3194 antibodies cross-neutralized SARS-CoV-2 variants of concern, including Omicron BA.1 and BA.2. Cv2.1169, isolated from a mucosa-derived IgA memory B cell demonstrated potency boost as IgA dimers and therapeutic efficacy as IgG antibodies in animal models. Structural data provided mechanistic clues to Cv2.1169 potency and breadth. Thus, potent broadly neutralizing IgA antibodies elicited in mucosal tissues can stem SARS-CoV-2 infection, and Cv2.1169 and Cv2.3194 are prime candidates for COVID-19 prevention and treatment.
Published: 2022

2. Molecular characterization of a new highly divergent Mobala related arenavirus isolated from Praomys sp. rodents

Author: Huguette, Simo Tchetgna, Stephane, Descorps-Declère, Benjamin, Selekon, Aurelia, Kwasiborski, Mathias, Vandenbogaert, Jean-Claude, Manuguerra, Antoine, Gessain, Valérie, Caro, Emmanuel, Nakouné, Nicolas, Berthet, Centre for Research in Infectious Diseases [Yaoundé] (CRID), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Bangui, Cellule d'Intervention Biologique d'Urgence - Laboratory for Urgent Response to Biological Threats (CIBU), Institut Pasteur [Paris] (IP), Cellule d'Intervention Biologique d'Urgence (Centre National de Référence) - Laboratory for Urgent Response to Biological Threats (National Reference Center) (CIBU), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This study was supported by the World Organisation for Animal health (OIE) through the European Union (capacity building and surveillance for Ebola virus disease, EBO-SURSY, project reference: FOOD/2016/379-660). This project was also supported by the Chinese Academy of Sciences, a Shanghai Municipal Science and Technology Major Project (Grant No. 2019SHZDZX02) and External Cooperation Program of Chinese Academy of Sciences (Grant No. 153211KYSB20160001)., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Base Sequence, Bioinformatics, viruses, Science, Computational Biology, Arenavirus, Sequence Analysis, DNA, Article, Arenaviruses, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Animals, Arenaviridae Infections, Sequencing, Medicine, Murinae, Arenaviridae, Phylogeny
Abstract: International audience; Arenaviruses represent a family of viruses that are naturally present in rodents belonging to subfamily Murinae, Neotominae or Sigmodontinae. Except for Lassa virus, little information is available on other Old-World arenaviruses. Here, we describe strain AnRB3214, a virus isolated from a presumed Praomys sp. rodent in the Central African Republic in 1981 and assigned to Ippy virus based on antigenic similarity. The strain was simultaneously sequenced on Illumina NovaSeq 6000 and MinION Mk1B devices and analysed with various bioinformatics tools. We show that the best genome coverage and depth were obtained with the Kaiju and Minimap2 classification and identification tools, on either the MinION or the Illumina reads. The genetic analysis of AnRB3214 fragments showed 68% to 79% similarity with the Mobala and Gairo mammarenaviruses at the nucleic acid level. Strain AnRB3214 had a truncated nucleoprotein smaller than that of other Old World arenaviruses. Molecular clock analysis suggests that this strain diverged from Mobala virus at least 400 years ago. Finally, this study illustrates the importance of genomics in the identification of archived viruses and expands on the diversity of African arenaviruses, because strain AnRB3214 is either a variant or a close relative of Mobala virus, and not Ippy virus.
Published: 2021

3. Essential dynamic interdependence of FtsZ and SepF for Z-ring and septum formation in Corynebacterium glutamicum

Author: Quentin Gaday, Anne Marie Wehenkel, Adrià Sogues, Sylvain Trépout, Rosario Durán, Alexandre Chenal, Mathilde Ben Assaya, Martín Graña, Pedro M. Alzari, Mariano A. Martinez, Alexis Voegele, Patrick England, Ahmed Haouz, Michael S. VanNieuwenhze, Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Bioinformatics / Bioinformática [Montevideo], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Biochimie des Interactions Macromoléculaires / Biochemistry of Macromolecular Interactions, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Department of Chemistry, Indiana University, Indiana University [Bloomington], Indiana University System-Indiana University System, Biophysique Moléculaire (Plate-forme), Cristallographie (Plateforme) - Crystallography (Platform), Institut Curie [Paris], Chimie et modélisation pour la biologie du cancer (CMBC), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Analytical Biochemistry and Proteomics / Bioquímica y Proteómica Analíticas [Montevideo], This work was partially supported by grants from the Institut Pasteur (Paris), the CNRS (France) and the Agence Nationale de la Recherche (PhoCellDiv, ANR-18-CE11-0017-01). A.S. is part of the Pasteur-Paris University (PPU) International Ph.D Program, funded by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 665807. Q.G. was funded by MTCI Ph.D school (ED 563), A.V. was supported by a DIM MalInf (infectious diseases) grant. M.G. acknowledges support from Programa de Desarrollo de las Ciencias Básicas and Sistema Nacional de Investigación e Innovación, Uruguay., We thank A. Ducret for help with MicrobeJ, F. Gubellini for help with electron microscopy, M. Bott and M. Baumgart for the pk19-P3323-lcpA plasmid and help with corynebacterial genetics, and H. Gramajo for the pTGR5 plasmid. We gratefully acknowledge the core facilities at the Institut Pasteur C2RT, in particular G. Pehau-Arnaudet (UBI), B. Raynal, S. Brule (PFBMI), P. Weber, C. Pissis (PFC), and J. Fernandes (UtechS PBI/Imagopole, supported by France BioImaging, ANR-10–INSB–04, Investments for the Future). We thank the staff of ESRF and of EMBL-Grenoble for assistance and support in using beamlines ID30B and ID23-1, and the staff of SOLEIL Synchrotron for assistance in using the beamline Disco. We acknowledge the PICT-IBISA for providing access to the cryo-EM facility at Orsay. Finally, we would like to thank the reviewers for their coments and suggestions, which have helped us to improve the quality of the manuscript., ANR-18-CE11-0017,PhoCellDiv,Mécanismes moléculaires phospho-dépendants de l'assemblage et de la régulation du divisome bactérien(2018), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), BENEDIC, Bénédicte, APPEL À PROJETS GÉNÉRIQUE 2018 - Mécanismes moléculaires phospho-dépendants de l'assemblage et de la régulation du divisome bactérien - - PhoCellDiv2018 - ANR-18-CE11-0017 - AAPG2018 - VALID, Institut Pasteur International Docotal Program - PASTEURDOC - - H20202015-10-01 - 2020-10-01 - 665807 - VALID, Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cell division, [SDV]Life Sciences [q-bio], ved/biology.organism_classification_rank.species, Cell, General Physics and Astronomy, Plasma protein binding, physiological processes, Corynebacterium glutamicum, lcsh:Science, Peptide sequence, 0303 health sciences, Multidisciplinary, biology, Chemistry, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, biological phenomena, cell phenomena, and immunity, Dimerization, Cell division site, Protein Binding, Science, 030106 microbiology, Sequence alignment, macromolecular substances, Bacterial physiology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Bacterial Proteins, medicine, Amino Acid Sequence, Model organism, Mode of action, FtsZ, X-ray crystallography, 030304 developmental biology, 030306 microbiology, ved/biology, General Chemistry, Gene Expression Regulation, Bacterial, biology.organism_classification, Cytoskeletal proteins, 030104 developmental biology, biology.protein, bacteria, lcsh:Q, Sequence Alignment, Function (biology), Cytokinesis, Bacteria
Abstract: The mechanisms of Z-ring assembly and regulation in bacteria are poorly understood, particularly in non-model organisms. Actinobacteria, a large bacterial phylum that includes the pathogen Mycobacterium tuberculosis, lack the canonical FtsZ-membrane anchors and Z-ring regulators described for E. coli. Here we investigate the physiological function of Corynebacterium glutamicum SepF, the only cell division-associated protein from Actinobacteria known to interact with the conserved C-terminal tail of FtsZ. We show an essential interdependence of FtsZ and SepF for formation of a functional Z-ring in C. glutamicum. The crystal structure of the SepF–FtsZ complex reveals a hydrophobic FtsZ-binding pocket, which defines the SepF homodimer as the functional unit, and suggests a reversible oligomerization interface. FtsZ filaments and lipid membranes have opposing effects on SepF polymerization, indicating that SepF has multiple roles at the cell division site, involving FtsZ bundling, Z-ring tethering and membrane reshaping activities that are needed for proper Z-ring assembly and function., The mechanisms of Z-ring assembly and regulation in bacteria are poorly understood, particularly in non-model organisms. Here, Sogues et al. study the interaction between FtsZ and SepF in Corynebacterium glutamicum, showing an essential interdependence of these proteins for formation of a functional Z-ring.
Published: 2020

4. Case Report: Evolution of Humoral and Cellular Immunity in Two COVID-19 Breakthrough Infections After BNT162b2 Vaccine

Author: Floriane Gallais, Pierre Gantner, Delphine Planas, Morgane Solis, Timothée Bruel, Florian Pierre, Eric Soulier, Paola Rossolillo, Slim Fourati, Jean Sibilia, Olivier Schwartz, Samira Fafi-Kremer, Laboratoire de Virologie [Strasbourg], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Strasbourg, This work was supported by the Strasbourg University Hospital (SeroCoV-HUS, PRI 7782), ANR-18-CE17-0028, ANR-11-LABX-0070_TRANSPLANTEX, Strasbourg University and the Institut National de la Santé et de la Recherche Médicale (UMR_S 1109). Work in OS lab is funded by the Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. DP is supported by the Vaccine Research Institute., We are grateful to the participants of the study. We thank Dr. Negar Sedghi and Dr. Dominique Desprez for reporting us the breakthrough cases., ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: MESH: Humans, MESH: Middle Aged, SARS-CoV-2, Immunology, breakthrough infection, MESH: CD4-Positive T-Lymphocytes, MESH: Adult, MESH: Vaccination, MESH: CD8-Positive T-Lymphocytes, MESH: Antibodies, Neutralizing, MESH: COVID-19 Vaccines, vaccine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology and Allergy, MESH: COVID-19, MESH: SARS-CoV-2, MESH: Immune Evasion, MESH: BNT162 Vaccine, variant of concern, MESH: Female, MESH: Antibodies, Viral, immune evasion
Abstract: BackgroundSARS-CoV-2 breakthrough infections after complete vaccination are increasing whereas their determinants remain uncharacterized.MethodsWe analyzed two cases of post-vaccination SARS-CoV-2 infections by α and β variants, respectively. For each participant both humoral (binding and neutralizing antibodies) and cellular (activation markers and cytokine expression) immune responses were characterized longitudinally.ResultsThe first participant (P1) was infected by an α variant and displayed an extended and short period of viral excretion and symptom. Analysis of cellular and humoral response 72 h post-symptom onset revealed that P1 failed at developing neutralizing antibodies and a potent CD4 memory response (lack of SARS-CoV-2 specific CD4+IL-2+ cells) and CD8 effector response (CD8+IFNγ+ cells). The second participant (P2) developed post-vaccination SARS-CoV-2 infection by a β variant, associated with a short period of viral excretion and symptoms. Despite displaying initially high levels and polyfunctional T cell responses, P2 lacked initial β-directed neutralizing antibodies. Both participants developed and/or increased their neutralization activity and cellular responses against all variants, namely, β and δ variants that lasts up to 3 months after breakthrough infection.ConclusionsAn analysis of cellular and humoral response suggests two possible mechanisms of breakthrough infection: a poor immune response to vaccine and viral evasion to neutralizing antibodies.
Published: 2022

5. Severe relapse of SARS‐CoV‐2 infection in a kidney transplant recipient with negative nasopharyngeal SARS‐CoV‐2 RT‐PCR after rituximab

Author: Antoine Morel, Sandrine Imbeaud, Anne Scemla, Hélène Péré, Jacques Fourgeaud, Lucile Amrouche, Nicolas Robillard, Delphine Planas, Julien Puech, Sylvie Simon, Fanny Lanternier, Laurent Bélec, Julien Zuber, Olivier Schwartz, Dany Anglicheau, Nathalie Chavarot, David Veyer, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), The authors would like to thank AcaciaTools for their proofreading services, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris-Saclay, Service Néphrologie et transplantation rénale Adultes [CHU Necker], Université Sorbonne Paris Cité (USPC), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Vaccine Research Institute [Créteil, France] (VRI), Université Paris Cité (UPCité), Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Virologie [Hôpital Européen Georges Pompidou - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Transplantation, MESH: Humans, infection and infectious agents-viral, translational research/science, [SDV]Life Sciences [q-bio], infectious disease, MESH: COVID-19 Testing, kidney transplantation/nephrology, clinical research/practice, MESH: Kidney Transplantation, MESH: Recurrence, lung disease: infectious, MESH: Reverse Transcriptase Polymerase Chain Reaction, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology and Allergy, MESH: COVID-19, Pharmacology (medical), MESH: SARS-CoV-2, MESH: Rituximab
Abstract: International audience; Immunocompromised patients may experience prolonged viral shedding after their initial SARS-CoV-2 infection, however, symptomatic relapses after remission currently remain rare. We herein describe a severe COVID-19 relapse case of a kidney transplant recipient (KTR) following rituximab therapy, 3 months after a moderate COVID-19 infection, despite viral clearance after recovery of the first episode. During the clinical relapse, the diagnosis was established on a broncho-alveolar lavage specimen (BAL) by RT-PCR. The infectivity of the BAL sample was confirmed on a cell culture assay. Whole genome sequencing confirmed the presence of an identical stain (Clade 20A). However, it had an acquired G142D mutation and a larger deletion of 3-amino-acids at position 143-145. These mutations located within the N-terminal domain are suggested to play a role in viral entry. The diagnosis of a COVID-19 relapse should be considered in the setting of unexplained persistent fever and/or respiratory symptoms in KTRs (especially for those after rituximab therapy), even in patients with previous negative naso-pharyngeal SARS-CoV-2 PCR.
Published: 2022

6. Impact of booster vaccination on the control of COVID-19 Delta wave in the context of waning immunity: application to France in the winter 2021/22

Author: Paolo Bosetti, Cécile Tran Kiem, Alessio Andronico, Juliette Paireau, Daniel Levy-Bruhl, Lise Alter, Arnaud Fontanet, Simon Cauchemez, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Haute Autorité de Santé [Saint-Denis La Plaine] (HAS), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), We acknowledge financial support from the Investissement d’Avenir program, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program (grant ANR-10-LABX-62-IBEID), HAS, Santé Publique France, the EMERGEN project (ANRS0151), the INCEPTION project (PIA/ANR-16-CONV-0005), the European Union’s Horizon 2020 research and innovation program under grant 101003589 (RECOVER) and 874735 (VEO), AXA and Groupama., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 874735,H2020-SC1-2019-Single-Stage-RTD,VEO(2020), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), European Project: 874735,VEO, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Université Paris Cité (UPC)-Pasteur-Cnam Risques infectieux et émergents (PACRI), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Paris Cité (UPC)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM), and HESAM Université (HESAM)-HESAM Université (HESAM)-Université Paris Cité (UPC)
Subjects: 0303 health sciences, COVID-19 Vaccines, SARS-CoV-2, Epidemiology, Vaccination, Immunization, Secondary, Public Health, Environmental and Occupational Health, COVID-19, 3. Good health, modelling, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Seasons, 030212 general & internal medicine, Rapid Communication, 030304 developmental biology
Abstract: Europe has experienced a large COVID-19 wave caused by the Delta variant in winter 2021/22. Using mathematical models applied to Metropolitan France, we find that boosters administered to ≥ 65, ≥ 50 or ≥ 18 year-olds may reduce the hospitalisation peak by 25%, 36% and 43% respectively, with a delay of 5 months between second and third dose. A 10% reduction in transmission rates might further reduce it by 41%, indicating that even small increases in protective behaviours may be critical to mitigate the wave.
Published: 2022

7. COVID-19 outbreak in vaccinated patients from a haemodialysis unit: antibody titres as a marker of protection from infection

Author: Idris Boudhabhay, Alexandra Serris, Aude Servais, Delphine Planas, Aurélie Hummel, Bruno Guery, Perrine Parize, Claire Aguilar, Myriam Dao, Claire Rouzaud, Elsa Ferriere, Bertrand Knebelmann, Hamza Sakhi, Marianne Leruez, Dominique Joly, Olivier Schwartz, Fanny Lanternier, Timothée Bruel, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Néphrologie et transplantation rénale Adultes [CHU Necker], Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Virologie [CHU Necker], We thank William Henry Bolland for his critical reading of the manuscript and members of the Virus and Immunity Unit for discussions and help, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Transplantation, COVID-19 outbreak, hemodialysis, SARS-CoV-2, COVID-19, Viral Vaccines, Antibodies, Monoclonal, Humanized, Antibodies, Viral, Disease Outbreaks, Hemodialysis Units, Hospital, Nephrology, BNT162b2 mRNA vaccination, Renal Dialysis, Immunoglobulin G, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, monoclonal antibodies, humoral response, BNT162 Vaccine, Retrospective Studies
Abstract: Background Patients on maintenance haemodialysis (HD) have an increased risk of severe coronavirus disease 2019 (COVID-19) and a reduced response to vaccines. Data are needed to identify immune correlates of protection in this population. Methods Following a COVID-19 outbreak among vaccinated patients in a HD unit, clinical data and serological response to BNT162b2 vaccine were retrospectively recorded. Results Among 53 patients present in the dialysis room, 14 were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (COVID_Pos) and 39 were not. Compared with uninfected patients, COVID_Pos patients more frequently had additional causes of immunosuppression (50% versus 21%; P = .046) and were more often scheduled on the Monday–Wednesday–Friday (MWF) shift (86% versus 39%; P = .002). Moreover, COVID_Pos had lower anti-spike (S) immunoglobulin G (IgG) titres than uninfected patients {median 24 BAU/mL [interquartile range (IQR) 3–1163] versus 435 [99–2555]; P = .001} and lower neutralization titres [median 108 (IQR 17–224) versus 2483 (481–43 908); P = .007]. Anti-S and neutralization antibody titres are correlated (r = 0.92, P 284 BAU/mL got infected. Ten of 14 COVID_Pos patients were treated with casirivimab and imdevimab. No patient developed severe disease. Conclusions Anti-S IgG titre measured prior to exposure correlates to protection from SARS-CoV-2 infection in HD patients. BNT162b2 vaccination alone or in combination with monoclonal antibodies prevented severe COVID-19.
Published: 2021

8. Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques

Author: Zhiqing Wang, Olivier Schwartz, Mathieu Surenaud, Mireille Centlivre, Gerard Zurawski, Julien Lemaitre, Léa Dupaty, Christine Lacabaratz, Yves Levy, Rodolphe Thiébaut, Sylvie van der Werf, Inga Szurgot, Romain Marlin, Véronique Godot, Severin Coleon, Aurélie Wiedemann, Giuseppe Pantaleo, Pauline Maisonnasse, Delphine Planas, Mélanie Prague, Catherine Chapon, Mario Gomez-Pacheco, Thibaut Naninck, Mathilde Galhaut, Anne-Sophie Gallouet, Jerome Ellis, Mariangela Cavarelli, Sandra Zurawski, Nidhal Kahlaoui, Roger Le Grand, Timothée Bruel, Francis Relouzat, Craig Fenwick, Nathalie Dereuddre-Bosquet, Sylvain Cardinaud, Raphael Ho Tsong Fang, Peter Liljeström, Vanessa Contreras, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Baylor Scott & White Charles A. Sammons Cancer Center [Dallas, TX, USA], Lausanne University Hospital, Université de Lausanne = University of Lausanne (UNIL), Karolinska Institutet [Stockholm], Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris]-Université Paris Cité (UPCité), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Hôpital Henri Mondor, Hôpital Albert Chenevier, The programme was funded by the Vaccine Research Institute via the ANR-10-LABX-77 grant. Studies in hu-mice model have been supported by ARN grant ANR-20-COV6-0004-01. The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the 'Programme Investissements d’Avenir', managed by the ANR under reference ANR-11-INBS-0008. The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT’s facilities and imaging technologies. The NHP study received financial support from REACTing, the Fondation pour la Recherche Medicale (FRM, AM-CoV-Path) and the European Infrastructure TRANSVAC2 (730964) for implementation of in vivo imaging technologies an NHP immuno assays. The virus stock used in NHPs was obtained through the EVAg platform (https://www.european-virus-archive.com/), funded by H2020 (653316)., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-20-COV6-0004,DC-CoVaC,Développement de vaccins anti-SARS-CoV-2(2020), ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), European Project: 730964, H2020, RIA,H2020-INFRAIA-2016-1,TRANSVAC2(2017), European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), University of Lausanne (UNIL), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris], Vaccine Research Institute [Créteil, France] (VRI), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), DARMIGNY, SANDRINE, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Développement de vaccins anti-SARS-CoV-2 - - DC-CoVaC2020 - ANR-20-COV6-0004 - COVID-19 - VALID, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, European Vaccine Research and Development Infrastructure - TRANSVAC2 - - H2020, RIA2017-05-01 - 2022-04-30 - 730964 - VALID, and European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID
Subjects: T-Lymphocytes, medicine.medical_treatment, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Mice, 0302 clinical medicine, 030212 general & internal medicine, skin and connective tissue diseases, B-Lymphocytes, 0303 health sciences, Multidisciplinary, biology, Vaccination, 3. Good health, [SDV] Life Sciences [q-bio], Spike Glycoprotein, Coronavirus, Vaccines, Subunit, Antibody, Adjuvant, Protein vaccines, COVID-19 Vaccines, Science, Protein domain, Antigen-Presenting Cells, Virulence, Article, General Biochemistry, Genetics and Molecular Biology, Viral vector, 03 medical and health sciences, Protein Domains, medicine, Animals, Humans, CD40 Antigens, 030304 developmental biology, CD40, SARS-CoV-2, fungi, COVID-19, Convalescence, General Chemistry, Virology, body regions, Viral infection, Preclinical research, Reinfection, Mutation, Humanized mouse, biology.protein, Macaca
Abstract: Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children and pregnant women. Here, we present a new generation of subunit vaccines targeting viral antigens to CD40-expressing antigen-presenting cells. We demonstrate that targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to CD40 (αCD40.RBD) induces significant levels of specific T and B cells, with long-term memory phenotypes, in a humanized mouse model. Additionally, we demonstrate that a single dose of the αCD40.RBD vaccine, injected without adjuvant, is sufficient to boost a rapid increase in neutralizing antibodies in convalescent non-human primates (NHPs) exposed six months previously to SARS-CoV-2. Vaccine-elicited antibodies cross-neutralize different SARS-CoV-2 variants, including D614G, B1.1.7 and to a lesser extent B1.351. Such vaccination significantly improves protection against a new high-dose virulent challenge versus that in non-vaccinated convalescent animals., In this study, Marlin et al. provide insights into the potential use of subunit vaccines that induce a high level of protection against SARS-CoV-2 in animal models.
Published: 2021

9. Artemisinin-independent inhibitory activity of Artemisia sp. infusions against different Plasmodium stages including relapse-causing hypnozoites

Author: Valérie Soulard, Nathalie Dereuddre-Bosquet, Cyrille Y. Botté, Roger Le Grand, Nadia Amanzougaghene, Jean-François Franetich, Amélie Vantaux, Kutub Ashraf, Christophe-Sébastien Arnold, Benoit Witkowski, Mallaury Bordessoulles, Jean-Christophe Barale, Teun Bousema, Romain Duval, Georges Snounou, Guillaume Cazals, Shahin Tajeri, Geert-Jan van Gemert, Dominique Mazier, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Radboud University Medical Center [Nijmegen], Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris]-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPC), Malaria Translational Research Pasteur International Unit, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur [Paris] (IP), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), K Ashraf was supported by Labex ParaFrap-IRD PhD South program (ANR-11-LABX-0024). S Tajeri acknowledges postdoctoral funding support from Fondation pour la Recherche Médicale (FRM) for the PALUKILL project. N Amanzougaghene was supported by Agence nationale de la recherche, project Plasmodrug, and Fondation Sorbonne Université. The work performed by CY Botté and C-S Arnold are supported by Fondation pour la Recherche Médicale (FRM, EQU202103012700), Agence Nationale de la Recherche, France (grant ANR-21-CE44-0010-01, Project ApicoLipidAdapt), Région Auvergne Rhône Alpes (Grant AuRA IRICE GEMELI), Finovi program (Apicolipid project), Laboratoire d’Excellence Parafrap, France (grant ANR-11-LABX-0024), LIA-IRP CNRS Program (Apicolipid project), CEFIPRA-MESRI (Project 6003-1), IDEX Université Grenoble-Alpes and MESRI PhD program fellowship. The investigations on P. cynomolgi were funded through a grant from the Agence Nationale de la Recherche, France (ANR-17-CE13-0025-01), IDMIT infrastructure is supported by the French government 'Programme d’Investissements d’Avenir' (PIA), under grants ANR-11-INBS-0008 (INBS IDMIT). This work benefited from the support of Maison de l’Artémisia, ITMO I3M, as well as equipment and services from the CELIS cell culture core facility (Paris Brain Institute), a platform supported through the ANR grants, ANR-10-IAIHU-06 and ANR-11-INBS-0011-NeurATRIS, We would like to acknowledge the help of QUANT microscopy platform of the Paris Brain Institute specially David Akbar, Claire Lovo, and Aymeric Millécamps for their help in analysis of microscopic images and sporozoite motility videos. We thank Laurent Rénia, Noah Sather, Philippe Grellier, and Scott Lindner for the kind gift of anti-Plasmodium antibodies listed in the Materials and Methods section. The kind help of Sivchheng Phal and Chansophea Chhin (Institut Pasteur du Cambodge, Phnom Penh, Cambodia) with P. vivax experiments is sincerely thanked. We are grateful to Lucile Cornet-Vernet and Pierre Lutgen for providing us Artemisia plants., ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), ANR-18-CE18-0009,plasmodrug,Développement d'un nouvel antipaludique ciblant plusieurs étapes du cycle de Plasmodium(2018), ANR-21-CE44-0010,ApicoLipidAdapt,Elucider les mécanismes d'adaptation métaboliques et lipidiques du parasite Toxoplasma gondii en fonction de l'environnement nutritionnel de son hôte(2021), ANR-17-CE13-0025,IMHyp,Recherches sur l'Hypnozoïte du Paludisme(2017), ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011), Witkowski, Benoit, Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Développement d'un nouvel antipaludique ciblant plusieurs étapes du cycle de Plasmodium - - plasmodrug2018 - ANR-18-CE18-0009 - AAPG2018 - VALID, Elucider les mécanismes d'adaptation métaboliques et lipidiques du parasite Toxoplasma gondii en fonction de l'environnement nutritionnel de son hôte - - ApicoLipidAdapt2021 - ANR-21-CE44-0010 - AAPG2021 - VALID, Recherches sur l'Hypnozoïte du Paludisme - - IMHyp2017 - ANR-17-CE13-0025 - AAPG2017 - VALID, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, Infrastructures - Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences - - NeurATRIS2011 - ANR-11-INBS-0011 - INBS - VALID, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: artemisia afra, Plasmodium berghei, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Plasmodium vivax, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Drug resistance, Plant Science, Pharmacology, Artemisia annua, Plasmodium, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Parasite hosting, Artemisia annua, artemisia afra, Plasmodium cynomolgi, Plasmodium falciparum, Plasmodium berghei, hypnozoite, hepatic stage, Apicoplast, mitochondria, Artemisia afra, Artemisinin, 0303 health sciences, Ecology, biology, hepatic stage, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, mitochondria, [SDV] Life Sciences [q-bio], medicine.drug, Plasmodium cynomolgi, 030231 tropical medicine, Plasmodium falciparum, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biochemistry, Genetics and Molecular Biology (miscellaneous), 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Apicoplast, parasitic diseases, medicine, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, biology.organism_classification, medicine.disease, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Artemisia, Malaria, hypnozoite
Abstract: Artemisinin-based combination therapies (ACT) are the frontline treatments against malaria worldwide. Recently the use of traditional infusions fromArtemisia annua(from which artemisinin is obtained) orA. afra(lacking artemisinin) has been controversially advocated. Such unregulated plant-based remedies are strongly discouraged as they might constitute sub-optimal therapies and promote drug resistance. Here, we conducted the first comparative study of the anti-malarial effects of both plant infusionsin vitroagainst the asexual erythrocytic stages ofP. falciparumand the pre-erythrocytic (i. e., liver) stages of variousPlasmodiumspecies. Low concentrations of either infusion accounted for significant inhibitory activities across every parasite species and stage studied. We show that these antiplasmodial effects were essentially artemisinin-independent and were additionally monitored by observations of the parasite apicoplast and mitochondrion. In particular, the infusions significantly incapacitated sporozoites, and forP. vivaxandP. cynomolgi,disrupted the hypnozoites. This provides the first indication that compounds other than 8-aminoquinolines could be effective antimalarials against relapsing parasites. These observations advocate for further screening to uncover urgently needed novel antimalarial lead compounds.
Published: 2021

10. Actinobacteria challenge the paradigm: A unique protein architecture for a well-known, central metabolic complex

Author: Marco Bellinzoni, Pedro M. Alzari, Lu Yang, Eduardo M. Bruch, Bertrand Raynal, Alexandra Boyko, Norik Lexa-Sapart, Pierre Vilela, Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Wuhan Institute of Biological Products, Biophysique Moléculaire (plateforme) - Molecular Biophysics (platform), This work was funded by the Agence Nationale de la Recherche (ANR) through the projects SUPERCPLX (ANR-13-JSV8-0003) and METACTINO (ANR-18-CE92-0003), both granted to M.B., and by institutional grants from the Institut Pasteur and the CNRS., We are grateful to the core facilities at Institut Pasteur C2RT (Centre for Technological Resources and Research), in particular to A. Haouz, P. Weber, and C. Pissis (Crystallography), S. Brûlé and B. Baron (Molecular Biophysics), M. Matondo, T. Chaze, and T. Douché (Proteomics), and J.-M. Winter, S. Tachon, and M. Vos (NanoImaging). We also gratefully acknowledge F. Gubellini (Structural Microbiology Unit) for her help in EM sample preparation and J.J. Pierella Karlusich (Ecole Normale Superieure, Paris), A. Thureau (Synchrotron Soleil), and V. Bunik (Lomonosov University, Moscow) for many helpful discussions. The NanoImaging Core at Institut Pasteur was created with the help of a grant from the French Government’s 'Investissements d’Avenir' program (EQUIPEX CACSICE—'Centre d’analyse de systèmes complexes dans les environnements complexes,' ANR-11-EQPX-0008) and is acknowledged for support with cryo-EM sample preparation, image acquisition, and analysis. We also acknowledge the synchrotron sources Soleil (Saint-Aubin, France) and ESRF (Grenoble, France) for granting access to their facilities and their staff for helpful assistance on the respective beamlines., ANR-13-JSV8-0003,SUPERCPLX,Structure, fonction et régulation d'un supercomplexe métabolique clé chez les Actinobacteries(2013), ANR-18-CE92-0003,METACTINO,Déchiffrer la plasticité métabolique des Actinobactéries(2018), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Biochemical Phenomena, Molecular Conformation, Dehydrogenase, Computational biology, Crystallography, X-Ray, Actinobacteria, Metabolic engineering, 03 medical and health sciences, Pyruvate dehydrogenase complex, pyruvate dehydrogenase, Integrative structural biology, Pyruvic Acid, Protein oligomerization, Ketoglutarate Dehydrogenase Complex, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Gene, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Multidisciplinary, Bacteria, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 030302 biochemistry & molecular biology, Computational Biology, Mycobacterium tuberculosis, Biological Sciences, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Kinetics, Enzyme, chemistry, Acyltransferase, Macromolecular complexes, central metabolism, Plasmids
Abstract: International audience; α-oxoacid dehydrogenase complexes are large, tripartite enzymatic machineries carrying out key reactions in central metabolism. Extremely conserved across the tree of life, they have been, so far, all considered to be structured around a high–molecular weight hollow core, consisting of up to 60 subunits of the acyltransferase component. We provide here evidence that Actinobacteria break the rule by possessing an acetyltranferase component reduced to its minimally active, trimeric unit, characterized by a unique C-terminal helix bearing an actinobacterial specific insertion that precludes larger protein oligomerization. This particular feature, together with the presence of an odhA gene coding for both the decarboxylase and the acyltransferase domains on the same polypetide, is spread over Actinobacteria and reflects the association of PDH and ODH into a single physical complex. Considering the central role of the pyruvate and 2-oxoglutarate nodes in central metabolism, our findings pave the way to both therapeutic and metabolic engineering applications.
Published: 2021

11. A virus-derived microRNA targets immune response genes during SARS-CoV-2 infection

Author: Singh, Meetali, Chazal, Maxime, Quarato, Piergiuseppe, Bourdon, Loan, Malabat, Christophe, Vallet, Thomas, Vignuzzi, Marco, Van Der Werf, Sylvie, Behillil, Sylvie, Donati, Flora, Sauvonnet, Nathalie, Nigro, Giulia, Bourgine, Maryline, Jouvenet, Nolwenn, Cecere, Germano, Mécanismes de l'Hérédité épigénétique / Mechanisms of epigenetic inheritance, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Signalisation antivirale - Virus sensing and signaling, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Populations virales et Pathogenèse - Viral Populations and Pathogenesis, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Département de Biologie cellulaire et infection - Department of Cell Biology and infection (BCI), Microenvironnement et Immunité - Microenvironment and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris] (IP)-TheraVectys-Université Paris Cité (UPCité), This project has received funding from the URGENCE COVID-19 Institut Pasteur Fundraising Campaign. M.S. is supported by the Pasteur-Roux-Cantarini Postdoctoral Fellowship Program., We thank the members of the Pasteur COVID-19 Task Force, Christophe D’Enfert, Felix Rey, and Olivier Schwartz for scientific discussions and support during the realization of this project and Geneviève Millon for critical reading of the manuscript. We thank Slim El-khiari for providing the ORF7a nucleotide sequences of SARS-CoV-2 variants, and the Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09), IBISA, and the Illumina COVID-19 Projects’ offer. Finally, we thank the Hospital Henri Mondor (AP-HP), Iradj Sobhani, Jeanne Tran Van Nhieu, and Aurélien Amiot for human colonic tissue resection., CECERE, Germano, Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], and Institut Pasteur [Paris]-TheraVectys
Subjects: SARS-CoV-2, viruses, [SDV]Life Sciences [q-bio], fungi, Immunity, COVID-19, biochemical phenomena, metabolism, and nutrition, Argonaute, [SDV] Life Sciences [q-bio], MicroRNAs, interferon response, Humans, RNA, Viral, 3' Untranslated Regions, miRNA
Abstract: International audience; SARS-CoV-2 infection results in impaired interferon response in patients with severe COVID-19. However, how SARS-CoV-2 interferes with host immune responses is incompletely understood. Here, we sequence small RNAs from SARS-CoV-2-infected human cells and identify a microRNA (miRNA) derived from a recently evolved region of the viral genome. We show that the virus-derived miRNA produces two miRNA isoforms in infected cells by the enzyme Dicer, which are loaded into Argonaute proteins. Moreover, the predominant miRNA isoform targets the 3'UTR of interferon-stimulated genes and represses their expression in a miRNA-like fashion. Finally, the two viral miRNA isoforms were detected in nasopharyngeal swabs from COVID-19 patients. We propose that SARS-CoV-2 can potentially employ a virus-derived miRNA to hijack the host miRNA machinery, which could help to evade the interferon-mediated immune response.
Published: 2021

12. Seroprevalence of anti-SARS-CoV-2 IgG at the first epidemic peak in French Guiana, July 2020

Author: Anais Perilhou, Elodie Boizon, Dominique Rousset, Nathalie Clement, Antoine Enfissi, Véronique Servas, Didier Musso, Thierry Carage, Félix Djossou, Céline Michaud, E. Beillard, Christelle Alves Sarmento, Stephanie Eustache, Sarah Bailly, Simon Cauchemez, Jean-François Carod, Samantha James, Mélanie Gaillet, Claude Flamand, Henrik Salje, Celine Tourbillon, Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris], Laboratoire d'Analyses Médicales [Kourou], Eurofins Labazur, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Centre Hospitalier de l'Ouest Guyanais Franck Joly [Saint-Laurent-du-Maroni, Guyane Française], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Cambridge [UK] (CAM), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), This study was supported by the National Research Agency to CF, the 'European Regional Development Fund' (GY0027257) to CF, the 'Regional Health Agency of French Guiana' to CF and the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur to CF., Unité d'Epidémiologie [Cayenne, Guyane française], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de virologie [Cayenne, Guyane française], Laboratoire de biologie médicale [Cayenne, Guyane française] (LBM), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), This study was supported by the National Research Agency to CF, the 'European Regional Development Fund' (GY0027257) to CF, the 'Regional Health Agency of French Guiana' to CF and the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur to CF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, We are grateful to all field workers, collaborators, technical and medical staff from Health Centers Department of Cayenne Hospital Center and biological laboratories and health centers involved in the EPI-COVID-19 project. We thank Bhety LABEAU, David MOUA, Laetitia BREMAND, Sylvie ALOEPOE, Elisabeth CHAN from Institut Pasteur in French Guiana, Nathalie JOLLY from Clinical Core of the Center for Translational Research of Institut Pasteur. We also thank Sophie GAULIN, Lysiane ROMAIN, Véronique TOGNERI and Tadens MPWENE from La Liberté., ANR-20-COVI-0014,EPI-COVID-19,Étude de la transmission intra-ménage autour des cas confirmés de COVID-19 en Guyane(2020), Flamand, Claude [0000-0002-8064-445X], Beillard, Emmanuel [0000-0002-2546-7614], Michaud, Céline [0000-0001-5410-6298], Cauchemez, Simon [0000-0001-9186-4549], Apollo - University of Cambridge Repository, and Salje, Henrik [0000-0003-3626-4254]
Subjects: RNA viruses, Viral Diseases, Pulmonology, Coronaviruses, Physiology, RC955-962, 030204 cardiovascular system & hematology, Antibodies, Viral, Serology, MESH: Aged, 80 and over, Medical Conditions, 0302 clinical medicine, Seroepidemiologic Studies, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Arctic medicine. Tropical medicine, MESH: Child, Pandemic, MESH: COVID-19, Medicine, 030212 general & internal medicine, [MATH]Mathematics [math], Enzyme-Linked Immunoassays, Child, Pathology and laboratory medicine, Virus Testing, MESH: Immunoglobulin G, MESH: Aged, Aged, 80 and over, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, Medical microbiology, Middle Aged, MESH: Infant, French Guiana, 3. Good health, Bioassays and Physiological Analysis, Infectious Diseases, Physiological Parameters, MESH: Young Adult, Child, Preschool, Viruses, Public aspects of medicine, RA1-1270, SARS CoV 2, Pathogens, Research Article, Adult, SARS coronavirus, Adolescent, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Research and Analysis Methods, Microbiology, Respiratory Disorders, Young Adult, 03 medical and health sciences, MESH: Cross-Sectional Studies, Diagnostic Medicine, MESH: French Guiana, Humans, Seroprevalence, MESH: SARS-CoV-2, Immunoassays, Enzyme Assays, Aged, MESH: Adolescent, Medicine and health sciences, MESH: Humans, MESH: Seroepidemiologic Studies, Routine screening, Biology and life sciences, SARS-CoV-2, business.industry, MESH: Child, Preschool, Body Weight, Organisms, Viral pathogens, Public Health, Environmental and Occupational Health, COVID-19, Infant, Spike Protein, MESH: Adult, Covid 19, Microbial pathogens, Cross-Sectional Studies, Young population, Immunoglobulin G, Respiratory Infections, Immunologic Techniques, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Biochemical Analysis, business, MESH: Antibodies, Viral, Demography
Abstract: Background While Latin America has been heavily affected by the pandemic, only a few seroprevalence studies have been conducted there during the first epidemic wave in the first half of 2020. Methodology/Principal findings A cross-sectional survey was performed between 15 July 2020 and 23 July 2020 among individuals who visited 4 medical laboratories or 5 health centers for routine screening or clinical management, with the exception of symptomatic suggestive cases of covid-19. Samples were screened for the presence of anti-SARS-CoV-2 IgG directed against domain S1 of the SARS-CoV-2 spike protein using the anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from Euroimmun. Conclusions/Significance The overall seroprevalence was 15.4% [9.3%-24.4%] among 480 participants, ranging from 4.0% to 25.5% across the different municipalities. The seroprevalence did not differ according to gender (p = 0.19) or age (p = 0.51). Among SARS-CoV-2 positive individuals, we found that 24.6% [11.5%-45.2%] reported symptoms consistent with COVID-19. Our findings revealed high levels of infection across the territory but a low number of resulting deaths, which can be explained by French Guiana’s young population structure., Author summary While Latin America has been heavily affected by the pandemic, only a few seroprevalence studies have been conducted there during the first epidemic wave in the first half of 2020. A cross-sectional survey was performed between 15 July 2020 and 23 July 2020 among individuals who visited 4 medical laboratories or 5 health centers for routine screening or clinical management, with the exception of symptomatic suggestive cases of covid-19. Samples were screened for the presence of anti-SARS-CoV-2 IgG using the anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from Euroimmun. The overall seroprevalence was 15.4% [9.3%-24.4%] among 480 participants, ranging from 4.0% to 25.5% across the different municipalities. The seroprevalence did not differ according to gender (p = 0.19) or age (p = 0.51). Among SARS-CoV-2 positive individuals, we found that 24.6% [11.5%-45.2%] reported symptoms consistent with COVID-19. Our findings revealed high levels of infection across the territory but a low number of resulting deaths, which can be explained by French Guiana’s young population structure.
Published: 2021

13. Malaria Parasite Stress Tolerance Is Regulated by DNMT2-Mediated tRNA Cytosine Methylation

Author: Paola B. Arimondo, Frédéric Bonhomme, Benoit Arcangioli, Flore Nardella, Elie Hammam, Jiaqi Liang, Artur Scherf, Peter C. Dedon, Diane Erdmann, Peter R. Preiser, Sebastian Baumgarten, Ameya Sinha, Samia Miled, Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Singapore-MIT Alliance for Research and Technology (SMART), Massachusetts Institute of Technology (MIT), Nanyang Technological University [Singapour], Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École Technique Supérieure du Laboratoire [Paris] (ETSL), Chimie biologique épigénétique - Epigenetic Chemical Biology (EpiCBio), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ecole doctorale Médicament -Toxicologie - Chimie - Imageries [Université de Paris] (ED 563), Université Paris Cité (UPCité), Dynamique du Génome - Dynamics of the genome, A. Sinha and J.L. acknowledge support from the Singapore‐MIT Alliance (SMA) Graduate Fellowship and MOE Tier 2 grant MOE2018-T2-2-131. Proteomics work was performed in part in the Center for Environmental Health Sciences BioCore, which is supported by Center grant P30‐ES002109 from the National Institute of Environmental Health Sciences. We also acknowledge Peiying Ho and Tan Tse Mien for providing support at SMART laboratories in Singapore. F.N. is supported by a Pasteur Cantarini fellowship. A. Sinha acknowledges financial support from the Singapore-MIT Alliance (SMA) Graduate Fellowships. P.B.A. acknowledges the DIM1Health 2019 grant from the Région Ile de France to the project EpiK for the LC/MS-MS equipment. This work was supported by the French Parasitology consortium ParaFrap (ANR-11-LABX0024) to A. Scherf, a Fondation Pasteur Swiss grant to A. Scherf, and an ANR grant (ANR-2019 EpiKillMal)., ANR-20-CE18-0006,EpiKillMal,Cibler la méthylation de l'ADN pour contrer la chimiorésistance du paludisme(2020), School of Biological Sciences, Singapore-MIT Alliance for Research and Technology, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Arimondo, Paola B, and Cibler la méthylation de l'ADN pour contrer la chimiorésistance du paludisme - - EpiKillMal2020 - ANR-20-CE18-0006 - AAPG2020 - VALID
Subjects: [SDV]Life Sciences [q-bio], Bisulfite sequencing, Protozoan Proteins, Epitranscriptomic, Epigenome, RNA, Transfer, homeostasis, Malaria, Falciparum, RNA Processing, Post-Transcriptional, Genetics, 0303 health sciences, biology, 030302 biochemistry & molecular biology, Biological sciences [Science], Translation (biology), epitranscriptomic, QR1-502, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Codon usage bias, DNA methylation, RNA, Protozoan, Research Article, TRNA modification, Plasmodium falciparum, malaria, Microbiology, DNA methyltransferase, 03 medical and health sciences, Cytosine, Stress, Physiological, RNA cytosine methylation, Virology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, tRNA, 030304 developmental biology, RNA, DNMT2, Methyltransferases, stress response, DNA Methylation, biology.organism_classification, Malaria, tRNA cytosine methylation, tRNA modification
Abstract: Malaria parasites need to cope with changing environmental conditions that require strong countermeasures to ensure pathogen survival in the human and mosquito hosts. The molecular mechanisms that protect Plasmodium falciparum homeostasis during the complex life cycle remain unknown. Here, we identify cytosine methylation of tRNAAsp (GTC) as being critical to maintain stable protein synthesis. Using conditional knockout (KO) of a member of the DNA methyltransferase family, called Pf-DNMT2, RNA bisulfite sequencing demonstrated the selective cytosine methylation of this enzyme of tRNAAsp (GTC) at position C38. Although no growth defect on parasite proliferation was observed, Pf-DNMT2KO parasites showed a selective downregulation of proteins with a GAC codon bias. This resulted in a significant shift in parasite metabolism, priming KO parasites for being more sensitive to various types of stress. Importantly, nutritional stress made tRNAAsp (GTC) sensitive to cleavage by an unknown nuclease and increased gametocyte production (>6-fold). Our study uncovers an epitranscriptomic mechanism that safeguards protein translation and homeostasis of sexual commitment in malaria parasites. IMPORTANCE P. falciparum is the most virulent malaria parasite species, accounting for the majority of the disease mortality and morbidity. Understanding how this pathogen is able to adapt to different cellular and environmental stressors during its complex life cycle is crucial in order to develop new strategies to tackle the disease. In this study, we identified the writer of a specific tRNA cytosine methylation site as a new layer of epitranscriptomic regulation in malaria parasites that regulates the translation of a subset of parasite proteins (>400) involved in different metabolic pathways. Our findings give insight into a novel molecular mechanism that regulates P. falciparum response to drug treatment and sexual commitment. Ministry of Education (MOE) Published version A. Sinha and J.L. acknowledge support from the Singapore‐MIT Alliance (SMA) Graduate Fellowship and MOE Tier 2 grant MOE2018-T2-2-131. Proteomics work was performed in part in the Center for Environmental Health Sciences BioCore, which is supported by Center grant P30‐ES002109 from the National Institute of Environmental Health Sciences. F.N. is supported by a Pasteur Cantarini fellowship. A. Sinha acknowledges financial support from the Singapore-MIT Alliance (SMA) Graduate Fellowships. P.B.A. acknowledges the DIM1Health 2019 grant from the Région Ile de France to the project EpiK for the LC/MS-MS equipment. This work was supported by the French Parasitology consortium ParaFrap (ANR-11-LABX0024) to A. Scherf, a Fondation Pasteur Swiss grant to A. Scherf, and an ANR grant (ANR-2019 EpiKillMal).
Published: 2021

14. H3K9 tri-methylation at Nanog times differentiation commitment and enables the acquisition of primitive endoderm fate

Author: A. Chervova, Michel Cohen-Tannoudji, S. Vandormael-Pournin, L. Vincenti, Agnès Dubois, Pablo Navarro, Institut Pasteur [Paris], Epigénomique, Prolifération et Identité Cellulaire - Epigenomics, Proliferation and the Identity of Cells (EPIC), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), P.N. and M.C-T. acknowledge the Labex Revive (Investissement d’Avenir, ANR-10-LABX-73), the Institut Pasteur and the CNRS for funding., The authors acknowledge the cytometry platform of Institut Pasteur for technical assistance and L. Bally-Cuif and S. Tajbakhsh for critical reading of the manuscript., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Homeobox protein NANOG, 0303 health sciences, biology, Somatic cell, 030302 biochemistry & molecular biology, Embryonic stem cell, Cell biology, 03 medical and health sciences, Histone H3, Histone, embryonic structures, biology.protein, Gene silencing, Enhancer, Transcription factor, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030304 developmental biology
Abstract: Mouse Embryonic Stem (ES) cells have an inherent propensity to explore distinct gene-regulatory states associated with either self-renewal or differentiation. This property is largely dependent on ERK activity, which promotes silencing of pluripotency genes, most notably of the transcription factor Nanog. Here, we aimed at identifying repressive histone modifications that would mark the Nanog locus for inactivation in response to ERK activity. We found histone H3 lysine 9 tri-methylation (H3K9me3) focally enriched between the Nanog promoter and its −5kb enhancer. While in undifferentiated ES cells H3K9me3 at Nanog depends on ERK activity, in somatic cells it becomes ERK-independent. Moreover, upon deletion of the region harbouring H3K9me3, ES cells display reduced heterogeneity of NANOG expression, delayed commitment into differentiation and impaired ability to acquire a primitive endoderm fate. We suggest that establishment of irreversible H3K9me3 at specific master regulators allows the acquisition of particular cell fates during differentiation.
Published: 2021

15. A Nanog-dependent gene cluster initiates the specification of the pluripotent epiblast

Author: Lorena Valverde Estrella, Yoan Renaud, Michel Cohen-Tannoudji, Claire Chazaud, Nicolas Allègre, Sabine Chauveau, Cynthia Dennis, Pierre Pouchin, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Embryon précoce de mammifères et cellules souches - Early Mammalian Development & Stem Cell Biology, Université Paris Cité (UPCité)-Epigénomique, Prolifération et Identité Cellulaire - Epigenomics, Proliferation and the Identity of Cells (EPIC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche(ANR-14CE11-0017 PrEpiSpec, ANR-10-LABX-73-01 REVIVE)Institut Pasteur, ANR-14-CE11-0017,Prepispec,Mécanismes moléculaires de la spécification des lignages cellulaires pendant l'embryogenèse précoce de la souris(2014), ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), Cohen-Tannoudji, Michel, Appel à projets générique - Mécanismes moléculaires de la spécification des lignages cellulaires pendant l'embryogenèse précoce de la souris - - Prepispec2014 - ANR-14-CE11-0017 - Appel à projets générique - VALID, Laboratoires d'excellence - Stem Cells in Regenerative Biology and Medicine - - REVIVE2010 - ANR-10-LABX-0073 - LABX - VALID, Epigénomique, Prolifération et Identité Cellulaire - Epigenomics, Proliferation and the Identity of Cells (EPIC), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Homeobox protein NANOG, 0303 health sciences, Embryo, Biology, Fibroblast growth factor, Embryonic stem cell, Cell biology, 03 medical and health sciences, 0302 clinical medicine, Epiblast, FGF4, [SDV.BDD] Life Sciences [q-bio]/Development Biology, embryonic structures, Inner cell mass, Induced pluripotent stem cell, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030217 neurology & neurosurgery, reproductive and urinary physiology, 030304 developmental biology
Abstract: SummaryThe epiblast (Epi) is the source of embryonic stem (ES) cells and all embryonic tissues. It differentiates alongside the primitive endoderm (PrE) in a randomly distributed “salt and pepper” pattern from the inner cell mass (ICM) during preimplantation of the mammalian embryo. NANOG and GATA6 are key regulators of this binary differentiation event, which is further modulated by heterogeneous FGF signalling. When and how Epi and PrE lineage specification is initiated within the developing embryo is still unclear. Here we generated NANOG and GATA6 double KO (DKO) mouse embryos and performed single-cell expression analyses. We found that the ICM was unable to differentiate in theDKOmice, allowing us to characterize the ICM precursor state. The normally heterogeneous expression ofFgf4between cells was significantly reduced inDKOICMs, impairing FGF signalling. In contrast, several pluripotency markers did still display cell-to-cell expression variability inDKOICMs. This revealed a primary heterogeneity independent of NANOG, GATA6 and FGF signalling that may also be conserved in humans. We found that NANOG is key in the initiation of epiblast specification already between the 16- and 32-cell stages, enabling the cell-clustered expression of many pluripotency genes. Our data uncover previously unknown biology in the early mouse embryo with potential implications for the field of pluripotent stem cells in human and other mammals.
Published: 2021

16. Release of infectious virus and cytokines in nasopharyngeal swabs from individuals infected with non-alpha or alpha SARS-CoV-2 variants: an observational retrospective study

Author: Monel, Blandine, Planas, Delphine, Grzelak, Ludivine, Smith, Nikaïa, Robillard, Nicolas, Staropoli, Isabelle, Goncalves, Pedro, Porrot, Françoise, Guivel-Benhassine, Florence, Guinet, Nathalie Demory, Rodary, Julien, Puech, Julien, Euzen, Victor, Bélec, Laurent, Orvoen, Galdric, Nunes, Léa, Moulin, Véronique, Fourgeaud, Jacques, Wack, Maxime, Imbeaud, Sandrine, Campagne, Pascal, Duffy, Darragh, Di Santo, James, Bruel, Timothée, Péré, Hélène, Veyer, David, Schwartz, Olivier, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Cité (UPCité), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Vaugirard-Gabriel Pallez, Hôpital Corentin Celton [Issy-les-Moulineaux], Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Work in OS lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR, Fondation pour la Recherche Médicale. DP is supported by the Vaccine Research Institute. LG is supported by the French Ministry of Higher Education, Research and Innovation. DD and JDS are funded by the ANR-20-COVI-0053 grant., We thank Maaran Michael Rajah, Nicoletta Casartelli, Michael White and Jeremy Dufloo for discussion and critical reading of the manuscript. We thank AGEPS, Assistance Publique - Hôpitaux de Paris, for providing the RDTs. We thank the patients who participated in the study, the clinical staff involved in their management, Théo Hirsch for stimulating discussions. We thank members of the Virus and Immunity Unit for discussion and help, Nathalie Aulner and the UtechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis, and Cyril Planchais & Hugo Mouquet for the kind gift of mAb48., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-20-COVI-0053,CoVarImm,Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence(2020), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Institut Pasteur [Paris]-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), École pratique des hautes études (EPHE), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)
Subjects: Adult, Male, Nasal swabs, Medicine (General), variants, Research paper, SARS-CoV-2, COVID-19, Middle Aged, Antibodies, Viral, Immunoglobulin A, infectious particles, R5-920, Immunoglobulin G, Nasopharynx, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Cytokines, Humans, Female, Aged, Retrospective Studies
Abstract: Background: The dynamics of SARS-CoV-2 alpha variant shedding and immune responses at the nasal mucosa remain poorly characterised. Methods: We measured infectious viral release, antibodies and cytokines in 426 PCR+ nasopharyngeal swabs from individuals harboring non-alpha or alpha variants. Findings: With both lineages, viral titers were variable, ranging from 0 to >106 infectious units. Rapid antigenic diagnostic tests were positive in 94% of samples with infectious virus. 68 % of individuals carried infectious virus within two days after onset of symptoms. This proportion decreased overtime. Viable virus was detected up to 14 days. Samples containing anti-spike IgG or IgA did not generally harbor infectious virus. Ct values were slightly but not significantly lower with alpha. This variant was characterized by a fast decrease of infectivity overtime and a marked release of 13 cytokines (including IFN-b, IP-10 and IL-10). Interpretation: The alpha variant displays modified viral decay and cytokine profiles at the nasopharyngeal mucosae during symptomatic infection. Funding: This retrospective study has been funded by Institut Pasteur, ANRS, Vaccine Research Institute, Labex IBEID, ANR/FRM and IDISCOVR, Fondation pour la Recherche Médicale.
Published: 2021

17. The cnf1 gene is associated to an expanding Escherichia coli ST131 H30Rx/C2 sublineage and confers a competitive advantage for host colonization

Author: Glaser, Mettouchi, Tsoumtsa Meda, Descorps-Declere, Nahori, Denamur, Ramirez Finn, Landraud, Lemichez, Dussurget, Patino-Navarete, Petracchini, Perthame, Ingersoll, Toxines bactériennes - Bacterial Toxins, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Paris (UP), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Inflammation et immunité des muqueuses, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Yersinia, Institut Pasteur [Paris], Laboratoire de Génétique Moléculaire [Hôpital Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by the 'Fondation ARC' PJA 20191209650, the 'Fondation pour la Recherche Médicale' (Equipe FRM 2016, DEQ20161136698), Ligue Nationale contre le Cancer Subvention de Recherche Scientifique, RS20/75-63 and the French National Research Agency (ANR-10-LABX-62-IBEID, INCEPTION) and ANR-17-CE17-0014. The plasmid pKOBEG was kindly provided by Jean-Marc Ghigo., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université Paris Cité (UPCité), Inflammation et immunité des muqueuses - Mucosal Inflammation and Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Genetics, 0303 health sciences, Gastrointestinal tract, Lineage (genetic), 030306 microbiology, [SDV]Life Sciences [q-bio], Mutant, Virulence, Biology, medicine.disease_cause, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Multiple drug resistance, 03 medical and health sciences, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine, Allele, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Gene, Escherichia coli, 030304 developmental biology
Abstract: SUMMARYEpidemiological projections point to acquisition of ever-expanding multidrug resistance (MDR) byEscherichia coli, a commensal of the digestive tract acting as a source of urinary tract pathogens. We performed a high-throughput genetic screening of predominantly clinicalE. coliisolates from wide geographical origins. This revealed a preferential distribution of the Cytotoxic Necrotizing Factor 1 (CNF1)-toxin encoding gene,cnf1, in four sequence types encompassing the pandemicE. coliMDR lineage ST131. This lineage is responsible for a majority of extraintestinal infections that escape first-line antibiotic treatment and has known enhanced capacities to colonize the gastrointestinal tract (GIT). Statistical modeling uncovered a dominant global expansion ofcnf1-positive strains within multidrug-resistant ST131 subcladeH30Rx/C2. Despite the absence of phylogeographical signals,cnf1-positive isolates adopted a clonal distribution into clusters on the ST131-H30Rx/C2 phylogeny, sharing a similar profile of virulence factors and the samecnf1allele. Functional analysis of thecnf1-positive clinical strain EC131GY ST131-H30Rx/C2, established that acnf1-deleted EC131GY is outcompeted by the wildtype strain in a mouse model of competitive infection of the bladder while both strains behave similarly during monoinfections. This points for positive selection ofcnf1during UTI rather than urovirulence. Wildtype EC131GY also outcompeted the mutant when concurrently inoculated into the gastrointestinal tract, arguing for selection within the gut. Whatever the site of selection, these findings support that the benefit ofcnf1enhancing host colonization by ST131-H30Rx/C2 in turn drives a worldwide dissemination of thecnf1gene together with extended spectrum of antibiotic resistance genes.
Published: 2021

18. Molecular organization and mechanics of single vimentin filaments revealed by super-resolution imaging

Author: Quang D. Tran, Christophe Zimmer, Jean-Yves Tinevez, Gérard Pehau-Arnaudet, Grégory Giannone, Cécile Leduc, Filipe Nunes Vicente, Mickaël Lelek, Sandrine Etienne-Manneville, Interdisciplinary Institute for Neuroscience [Bordeaux] (IINS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation - Imaging and Modeling, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Hub d'analyse d'images - Image Analysis Hub (Platform) (IAH), Institut Pasteur [Paris]-Université Paris Cité (UPC), Polarité cellulaire, Migration et Cancer - Cell Polarity, Migration and Cancer, Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Centre National de la Recherche Scientifique (CNRS), Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris], We gratefully acknowledge Audrey Salles and the Imagopole of Institut Pasteur (Paris), and the financial support of the Institut Pasteur (Paris), the France–BioImaging infrastructure network supported by the French National Research Agency (ANR-10-INSB-04, Investments for the future), and the Région Ile-de-France (program DIM-Malinf) for the use of the Elyra microscope and for funding the development of a dual objective STORM system (‘NANOINF’ project). This work was supported by the French National Research Agency ANR-16-CE13-0019, the Ligue contre le cancer (EL2017.LNCC), the Centre National de la Recherche Scientifique and Institut Pasteur., ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-16-CE13-0019,SiFi2Net,Filaments intermédiaires: du filament unique au réseau(2016), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut Pasteur [Paris] (IP)
Subjects: 0303 health sciences, Multidisciplinary, Structural organization, Materials science, biology, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Cellular functions, Vimentin, macromolecular substances, Superresolution, Protein filament, 03 medical and health sciences, 0302 clinical medicine, Molecular level, Microscopy, biology.protein, Biophysics, Intermediate filament, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Intermediate filaments (IF) are involved in key cellular functions including polarization, migration, and protection against large deformations. These functions are related to their remarkable ability to extend without breaking, a capacity that should be determined by the molecular organization of subunits within filaments. However, this structure-mechanics relationship remains poorly understood at the molecular level. Here, using super-resolution microscopy (SRM), we show that vimentin filaments exhibit a ~49 nm axial repeat both in cells and in vitro. As unit-length-filaments (ULFs) were measured at ~59 nm, this demonstrates a partial overlap of ULFs during filament assembly. Using an SRM-compatible stretching device, we also provide evidence that the extensibility of vimentin is due to the unfolding of its subunits and not to their sliding, thus establishing a direct link between the structural organization and its mechanical properties. Overall, our results pave the way for future studies of IF assembly, mechanical and structural properties in cells.
Published: 2021

19. Prevalence of ExoY Activity in Pseudomonas aeruginosa Reference Panel Strains and Impact on Cytotoxicity in Epithelial Cells

Author: Silistre, Hazel, Raoux-Barbot, Dorothée, Mancinelli, Federica, Sangouard, Flora, Dupin, Alice, Belyy, Alexander, Deruelle, Vincent, Renault, Louis, Ladant, Daniel, Touqui, Lhousseine, Mechold, Undine, Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Département de Biologie structurale et Chimie - Department of Structural Biology and Chemistry, Institut Pasteur [Paris], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Biochimie des Interactions Macromoléculaires / Biochemistry of Macromolecular Interactions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANR-18-CE44-0004,activExoY,Role et spécificités fonctionnelles des facteurs de virulence de type ExoY à activité Nucléotidyl Cyclase dépendante de l'actine dans les infections de bactéries à Gram-négatif(2018), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gestionnaire, HAL Sorbonne Université 5, and APPEL À PROJETS GÉNÉRIQUE 2018 - Role et spécificités fonctionnelles des facteurs de virulence de type ExoY à activité Nucléotidyl Cyclase dépendante de l'actine dans les infections de bactéries à Gram-négatif - - activExoY2018 - ANR-18-CE44-0004 - AAPG2018 - VALID
Subjects: cystic fibrosis, cGMP, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, ExoY, Pseudomonas aeruginosa, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Microbiology, nucleotidyl cyclase, Original Research
Abstract: International audience; ExoY is among the effectors that are injected by the type III secretion system (T3SS) of Pseudomonas aeruginosa into host cells. Inside eukaryotic cells, ExoY interacts with F-actin, which stimulates its potent nucleotidyl cyclase activity to produce cyclic nucleotide monophosphates (cNMPs). ExoY has broad substrate specificity with GTP as a preferential substrate in vitro. How ExoY contributes to the virulence of P. aeruginosa remains largely unknown. Here, we examined the prevalence of active ExoY among strains from the international P. aeruginosa reference panel, a collection of strains that includes environmental and clinical isolates, commonly used laboratory strains, and sequential clonal isolates from cystic fibrosis (CF) patients and thus represents the large diversity of this bacterial species. The ability to secrete active ExoY was determined by measuring the F-actin stimulated guanylate cyclase (GC) activity in bacterial culture supernatants. We found an overall ExoY activity prevalence of about 60% among the 40 examined strains with no significant difference between CF and non-CF isolates. In parallel, we used cellular infection models of human lung epithelial cells to compare the cytotoxic effects of isogenic reference strains expressing active ExoY or lacking the exoY gene. We found that P. aeruginosa strains lacking ExoY were in fact more cytotoxic to the epithelial cells than those secreting active ExoY. This suggests that under certain conditions, ExoY might partly alleviate the cytotoxic effects of other virulence factors of P. aeruginosa.
Published: 2021

20. Zika Virus Requires the Expression of Claudin-7 for Optimal Replication in Human Endothelial Cells

Author: Zoladek, Jim, Legros, Vincent, Jeannin, Patricia, Chazal, Maxime, Pardigon, Nathalie, Ceccaldi, Pierre-Emmanuel, Gessain, Antoine, Jouvenet, Nolwenn, Afonso, Philippe, Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Ecole Nationale Vétérinaire de Lyon (ENVL), Institut Pasteur [Paris], Signalisation antivirale - Virus sensing and signaling, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Université de Paris - UFR Sciences du Vivant [Sciences] (UP - UFR SDV), Université de Paris (UP), This work was supported by a Pasteur-Fiocruz grant and the 'Investissement d’Avenir' as part of a 'Laboratoire d’Excellence' (LabEx) French research program: Integrative Biology of Emerging Infectious Diseases (ANR10-LBX-62 IBEID). JZ was the recipient of a PhD fellowship from the ED562 – BioSPC and French ministry of education and research. VL was supported by a fellowship from the 'Fondation pour la Recherche Médicale' (FRM)., Microarray was performed by the Plateforme GenomEast of IGBMC, Illkirch, France. NS1 antibody was a kind gift from Marie Flamand (Institut Pasteur, Paris)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), UFR Sciences du Vivant [Sciences] - Université Paris Cité (UFR SDV UPCité), Université Paris Cité (UPCité), and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)
Subjects: flavivirus, [SDV]Life Sciences [q-bio], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, claudin, blood-brain barrier, Microbiology, endothelial cells, infection, Original Research, Zika virus
Abstract: The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb.2021.746589/full#supplementary-material; International audience; Zika virus (ZIKV) infection has been associated with a series of neurological pathologies. In patients with ZIKV-induced neurological disorders, the virus is detectable in the central nervous system. Thus, ZIKV is capable of neuroinvasion, presumably through infection of the endothelial cells that constitute the blood-brain barrier (BBB). We demonstrate that susceptibility of BBB endothelial cells to ZIKV infection is modulated by the expression of tight-junction protein claudin-7 (CLDN7). Downregulation of CLDN7 reduced viral RNA yield, viral protein production, and release of infectious viral particles in several endothelial cell types, but not in epithelial cells, indicating that CLDN7 implication in viral infection is cell-type specific. The proviral activity of CLDN7 in endothelial cells is ZIKV-specific since related flaviviruses were not affected by CLDN7 downregulation. Together, our data suggest that CLDN7 facilitates ZIKV infection in endothelial cells at a post-internalization stage and prior to RNA production. Our work contributes to a better understanding of the mechanisms exploited by ZIKV to efficiently infect and replicate in endothelial cells and thus of its ability to cross the BBB.
Published: 2021

21. Microfabricated Device for High-Resolution Imaging of Preimplantation Embryos

Author: Sandrine Vandormael-Pournin, Michel Cohen-Tannoudji, Samy Gobaa, Emmanuel Frachon, Embryon précoce de mammifères et cellules souches - Early Mammalian Development & Stem Cell Biology, Epigénomique, Prolifération et Identité Cellulaire - Epigenomics, Proliferation and the Identity of Cells (EPIC), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Plateforme technologique Biomatériaux et Microfluidique - Biomaterials and Microfluidics technologic Platform, Institut Pasteur [Paris], Katia Ancelin, Maud Borensztein, Université Paris Cité (UPCité)-Epigénomique, Prolifération et Identité Cellulaire - Epigenomics, Proliferation and the Identity of Cells (EPIC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)
Subjects: Photolithography, Transgene, Biology, Mouse embryo, Transgenic, law.invention, 03 medical and health sciences, Confocal microscopy, law, Live cell imaging, Microinjection, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030304 developmental biology, Live imaging, 0303 health sciences, Fluorescent reporter, Electroporation, 030302 biochemistry & molecular biology, Soft-Lithography, Embryo, Genetically modified organism, Cell biology, RNA microinjection, RNA electroporation, embryonic structures, Microfabricated cell culture devices, Ex vivo
Abstract: International audience; The mouse preimplantation embryo is an excellent system for studying how mammalian cells organize dynamically into increasingly complex structures. Accessible to experimental and genetic manipulations, its normal or perturbed development can be scrutinized ex vivo by real-time imaging from fertilization to late blastocyst stage. High-resolution imaging of multiple embryos at the same time can be compromised by embryos displacement during imaging. We have developed an inexpensive and easy-to-produce imaging device that facilitates greatly the imaging of preimplantation embryo. In this chapter, we describe the different steps of production and storage of the imaging device as well as its use for live imaging of mouse preimplantation embryos expressing fluorescent reporters from genetically modified alleles or after in vitro transcribed mRNA transfer by microinjection or electroporation.
Published: 2021

22. Epidemiology and control of SARS-CoV-2 epidemics in partially vaccinated populations: a modeling study applied to France

Author: Paolo Bosetti, Cécile Tran Kiem, Alessio Andronico, Vittoria Colizza, Yazdan Yazdanpanah, Arnaud Fontanet, Daniel Benamouzig, Simon Cauchemez, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Centre de sociologie des organisations (CSO), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), We acknowledge financial support from the Investissement d’Avenir program, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program (grant ANR-10-LABX-62-IBEID), HAS, Santé Publique France, the INCEPTION project(PIA/ANR-16-CONV-0005), the European Union’s Horizon 2020 research and innovation program under grant 101003589 (RECOVER) and 874735 (VEO), AXA and Groupama., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 874735,VEO, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège Doctoral, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), Centre de sociologie des organisations (Sciences Po, CNRS) (CSO), We acknowledge financial support from the Investissement d’Avenir program, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program (grant ANR-10-LABX-62-IBEID), HAS, Santé Publique France, the EMERGEN project (ANRS0151), the INCEPTION project (PIA/ANR-16-CONV-0005), the European Union’s Horizon 2020 research and innovation program under grant 101003589 (RECOVER) and 874735 (VEO), AXA and Groupama., European Project: 874735,H2020-SC1-2019-Single-Stage-RTD,VEO(2020), Sorbonne Université, Pasteur-Cnam risques infectieux et émergents (PACRI), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris], Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris], ANR-10-LABX-0062,IBEID,Biologie Intégrative des Maladies Infectieuses Emergentes(2011), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Benamouzig, Daniel, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, and Versatile Emerging infectious disease Observatory - VEO - - H2020-SC1-2019-Single-Stage-RTD2020-01-01 - 2024-12-31 - 874735 - VALID
Subjects: Adult, COVID-19 Vaccines, Adolescent, [SDV]Life Sciences [q-bio], [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, 030212 general & internal medicine, Child, Epidemics, 030304 developmental biology, 0303 health sciences, SARS-CoV-2, Non-pharmaceutical interventions, Vaccination, Infant, Newborn, COVID-19, Infant, General Medicine, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Child, Preschool, Medicine, Epidemiological Models, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SHS] Humanities and Social Sciences, France, Research Article
Abstract: Background Vaccination is expected to change the epidemiology and management of SARS-CoV-2 epidemics. Methods We used an age-stratified compartmental model calibrated to French data to anticipate these changes and determine implications for the control of an autumn epidemic. We assumed vaccines reduce the risk of hospitalization, infection, and transmission if infected by 95%, 60%, and 50%, respectively. Results In our baseline scenario characterized by basic reproduction number R0=5 and a vaccine coverage of 70–80–90% among 12–17, 18–59, and ≥ 60 years old, important stress on healthcare is expected in the absence of measures. Unvaccinated adults ≥60 years old represent 3% of the population but 43% of hospitalizations. Given limited vaccine coverage, children aged 0–17 years old represent a third of infections and are responsible for almost half of transmissions. Unvaccinated individuals have a disproportionate contribution to transmission so that measures targeting them may help maximize epidemic control while minimizing costs for society compared to non-targeted approaches. Of all the interventions considered including repeated testing and non-pharmaceutical measures, vaccination of the unvaccinated is the most effective. Conclusions With the Delta variant, vaccinated individuals are well protected against hospitalization but remain at risk of infection and should therefore apply protective behaviors (e.g., mask-wearing). Targeting non-vaccinated individuals may maximize epidemic control while minimizing costs for society. Vaccinating children protects them from the deleterious effects of non-pharmaceutical measures. Control strategies should account for the changing SARS-CoV-2 epidemiology.
Published: 2021

23. Peptoniphilus nemausensis sp. nov. a new Gram-positive anaerobic coccus isolated from human clinical samples, an emendated description of the genus Peptoniphilus and an evaluation of the taxonomic status of Peptoniphilus species with not validly published names

Author: Christelle Mazuet, Laure Diancourt, Michel R. Popoff, Alexis Criscuolo, Estelle Jumas-Bilak, Hélène Marchandin, Fabien Aujoulat, Cécilia Enault, Jean-Philippe Lavigne, Hydrosciences Montpellier (HSM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre National de Référence des Bactéries Anaérobies et Botulisme - National Reference Center Anaerobic Bacteria and Botulism (CNR), Institut Pasteur [Paris] (IP), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Toxines bactériennes - Bacterial Toxins, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Peptoniphilus, food.ingredient, Firmicutes, Biology, Applied Microbiology and Biotechnology, Microbiology, Human skin, Aesculin, 03 medical and health sciences, chemistry.chemical_compound, food, Type (biology), Genus, RNA, Ribosomal, 16S, Humans, Surgical Wound Infection, Anaerobiosis, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, Ecology, Evolution, Behavior and Systematics, Phylogeny, 030304 developmental biology, Gram, Genetics, 0303 health sciences, Diversity, Phylogenetic tree, 030306 microbiology, Strain (biology), Nucleic Acid Hybridization, Sequence Analysis, DNA, 16S ribosomal RNA, Bacterial Typing Techniques, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Polyphasic taxonomy, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Clinical isolate
Abstract: International audience; A Gram-positive, anaerobic coccus isolated from a human surgical site infection was previously shown to belong to an unknown species of the genus Peptoniphilus initially proposed as ‘Peptoniphilus nemausus’ sp. nov., based on both 16S rRNA gene sequence identity of 97.9% with the most closely related species Peptoniphilus coxii and an individualized phylogenetic branching within the genus Peptoniphilus. A polyphasic characterization of the novel species is proposed herein. Whole genome sequence analysis showed an average nucleotide identity value of 84.75% and digital DNA-DNA hybridization value of 28.9% against P. coxii type strain. The strain displayed unique features among members of the genus Peptoniphilus, as it was able to hydrolyze aesculin, and produced acetate as the major metabolic end-product without associated production of butyrate. Growth was observed under microaerophilic conditions. From all these data, the isolate is confirmed as belonging to a new Peptoniphilus species, for which the name Peptoniphilus nemausensis sp. nov. is proposed. The type strain is 1804121828T (= LMG 31466T = CECT 9935T). A database survey using a highly polymorphic partial sequence of the 16S rRNA gene of P. nemausensis revealed P. nemausensis to be a particularly rare skin-associated species in humans. An emendated description of the Peptoniphilus genus is proposed based on a review of the characteristics of the 12 new species with validly published names since the genus description in 2001 and of P. nemausensis. Finally, the relationships between members of the genus Peptoniphilus were explored based on whole genome sequence analysis in order to clarify the taxonomic status of not yet validly published species showing that three pairs of species should be considered as synonyms: Peptoniphilus timonensis and ‘Peptoniphilus phoceensis’, Peptoniphilus lacydonensis and ‘Peptoniphilus rhinitidis’, Peptoniphilus tyrrelliae and Peptoniphilus senegalensis.
Published: 2021

24. Conformational Insights into the Control of CNF1 Toxin Activity by Peptidyl-Prolyl Isomerization: A Molecular Dynamics Perspective

Author: Paillares, Eléa, Marechal, Maud, Swistak, Léa, Tsoumtsa Meda, Landry, Lemichez, Emmanuel, Malliavin, Thérèse, Toxines bactériennes - Bacterial Toxins, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université Sorbonne Paris Cité (USPC), Bioinformatique structurale - Structural Bioinformatics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), This work was financed by CNRS, INSERM, the Institut Pasteur, the INCEPTION project ANR-16-CONV-0005 , the ANR project ANR-19-ASTR-0001 and the joint ministerial program of Research and Development against Chemical, Biological, Radiological, Nuclear and Explosive risks (CBRNE). This work was also supported by the 'Fondation ARC' PJA 20191209650, the Ligue Nationale contre le Cancer Subvention de Recherche Scientifique RS20/75-63 and Oncomix research program and a DGA-MRIS/AID scholarship with Pasteur., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-19-ASTR-0001,ToxProtect_Larg_Spectr,Caractérisation d'un composé antitoxines bactériennes à large spectre(2019), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], QH301-705.5, Escherichia coli Proteins, Bacterial Toxins, Escherichia coli, X-Pro imide bond, peptidyl prolyl cis-trans isomerization, Molecular Dynamics Simulation, Article, CNF1, molecular dynamics, Molecular Docking Simulation, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Chemistry, Isomerism, Catalytic Domain, peptide docking, deamidase, Biology (General), [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], rhoA GTP-Binding Protein, QD1-999, Protein Binding
Abstract: The cytotoxic necrotizing factor 1 (CNF1) toxin from uropathogenic Escherichia coli constitutively activates Rho GTPases by catalyzing the deamidation of a critical glutamine residue located in the switch II (SWII). In crystallographic structures of the CNF1 catalytic domain (CNF1CD), surface-exposed P768 and P968 peptidyl-prolyl imide bonds (X-Pro) adopt an unusual cis conformation. Here, we show that mutation of each proline residue into glycine abrogates CNF1CD in vitro deamidase activity, while mutant forms of CNF1 remain functional on RhoA in cells. Using molecular dynamics simulations coupled to protein-peptide docking, we highlight the long-distance impact of peptidyl-prolyl cis-trans isomerization on the network of interactions between the loops bordering the entrance of the catalytic cleft. The energetically favorable isomerization of P768 compared with P968, induces an enlargement of loop L1 that fosters the invasion of CNF1CD catalytic cleft by a peptide encompassing SWII of RhoA. The connection of the P968 cis isomer to the catalytic cysteine C866 via a ladder of stacking interactions is alleviated along the cis-trans isomerization. Finally, the cis-trans conversion of P768 favors a switch of the thiol side chain of C866 from a resting to an active orientation. The long-distance impact of peptidyl-prolyl cis-trans isomerizations is expected to have implications for target modification.
Published: 2021

25. Immune checkpoint inhibitors increase T cell immunity during SARS-CoV-2 infection

Author: Jeremy Boussier, Olivier Peyrony, Majdi Jebali, Bruno Charbit, Benjamin Terrier, Nora Kramkimel, Céleste Lebbé, Aurélien Corneau, Magnus Fontes, Jérôme LeGoff, Selim Aractingi, Laetitia Da Meda, Frédéric Rieux-Laucat, Vincent Calmettes, P. Tetu, Olivier Schwartz, Laura Barnabei, Darragh Duffy, Nikaïa Smith, Clara Allayous, Jérôme Hadjadj, Timothée Bruel, Charles Cassius, Nader Yatim, Isabelle Staropoli, F. Herms, Catherine Blanc, Ludivine Grzelak, Barouyr Baroudjian, Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris]-Université Paris Cité (UPCité), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Laboratoire Roche [Boulogne-Billancourt], Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), N.Y. and C.L. acknowledge grant from the ARC Flash Covid-19 and Cancer call (ONCOVID). N.Y. and D.D. acknowledge grants from the Institut Pasteur for Covid-19 research and the ANR Flash Covid-19 call (CoVarImm). N.S. was supported by an Institut Pasteur Roux Cantarini fellowship. B.T. was supported by the Fonds IMMUNOV, for Innovation in Immunopathology. F.R.-L. acknowledges grants from the ANR Flash Covid-19 (AIROCOVID) and the FAST foundation. The study was also supported by the Institut National de la Santé et de la Recherche Médicale (Inserm) and by government grants managed by the Agence Nationale de la Recherche as part of the 'Investment for the future' program (ANR-10 IAHU-01 and ANR-18-RHUS-0010). L.B. was also supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) and is part of the Université de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its 'Investments for the future' program., ANR-20-COVI-0053,CoVarImm,Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence(2020), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018), ANR-17-EURE-0013,GENE,Génétique et Epigénétique Nouvelle Ecole(2017), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vougny, Marie-Christine, Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence - - CoVarImm2020 - ANR-20-COVI-0053 - COVID-19 - VALID, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation - - ATRACTION2018 - ANR-18-RHUS-0010 - RHUS - VALID, Génétique et Epigénétique Nouvelle Ecole - - GENE2017 - ANR-17-EURE-0013 - EURE - VALID, Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Paris (UP)
Subjects: Male, animal diseases, T-Lymphocytes, Adaptive Immunity, CD8-Positive T-Lymphocytes, Antibodies, Viral, Lymphocyte Activation, 0302 clinical medicine, Interferon, Prospective Studies, Immune Checkpoint Inhibitors, Melanoma, Research Articles, 0303 health sciences, Multidisciplinary, Effector, SciAdv r-articles, Middle Aged, Acquired immune system, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, medicine.drug, Research Article, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Immunology, Inflammation, chemical and pharmacologic phenomena, 03 medical and health sciences, Immune system, medicine, Humans, Health and Medicine, 030304 developmental biology, Aged, business.industry, SARS-CoV-2, COVID-19, biochemical phenomena, metabolism, and nutrition, medicine.disease, Coronavirus, bacteria, business, Immunologic Memory, CD8
Abstract: Immune checkpoint inhibitors for melanoma improve adaptive T cell immunity during COVID-19 without exacerbating inflammation., The COVID-19 pandemic has spread worldwide, yet the role of antiviral T cell immunity during infection and the contribution of immune checkpoints remain unclear. By prospectively following a cohort of 292 patients with melanoma, half of which treated with immune checkpoint inhibitors (ICIs), we identified 15 patients with acute or convalescent COVID-19 and investigated their transcriptomic, proteomic, and cellular profiles. We found that ICI treatment was not associated with severe COVID-19 and did not alter the induction of inflammatory and type I interferon responses. In-depth phenotyping demonstrated expansion of CD8 effector memory T cells, enhanced T cell activation, and impaired plasmablast induction in ICI-treated COVID-19 patients. The evaluation of specific adaptive immunity in convalescent patients showed higher spike (S), nucleoprotein (N), and membrane (M) antigen-specific T cell responses and similar induction of spike-specific antibody responses. Our findings provide evidence that ICI during COVID-19 enhanced T cell immunity without exacerbating inflammation.
Published: 2021

26. Discriminant value of repetitive behaviors in families with autism spectrum disorder and obsessional compulsive disorder probands

Author: Daniel Umbricht, Manuel Bouvard, Frédérique Amsellem, Marion Leboyer, Myriam Ly-Le Moal, Anita Beggiato, Lorraine Murtagh, Richard Delorme, Thomas Bourgeron, Aline Lefebvre, Alicia Cohen, Christopher H. Chatham, Anouck Amestoy, Anna Maruani, Service psychiatrique de l'enfant et de l'adolescent [CHU Hôpital Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Centre Ressources Autisme et Troubles du Développement (CRA), Hôpital Charles Perrens, UFR Sciences médicales 3 [Bordeaux], Laboratoire Roche [Boulogne-Billancourt], Roche Pharma Research and Early Development [Basel] (pRED), F. Hoffmann-La Roche [Basel], Fondation FondaMental [Créteil], Pôle de psychiatrie et d'addictologie des Hôpitaux Universitaires Henri-Mondor [Créteil], Centre hospitalier universitaire Henri-Mondor [Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This study is a part of clinical trial C07-33 sponsored by INSERM. It was financially supported by the funding of the Institut Pasteur, INSERM, the Fondation FondaMental, the APHP, the DHU Protect, the Fondation de France, the Labex BioPsy, the Fondation pour la Recherche Médicale and by the Roche Institute for Research and Translational Medicine, of the Investissements d'Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02, ANR-10-COHO-10-01, ANR-12-SAMA-0014, by the French National Center for Scientific Research (CNRS)., ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010), ANR-12-SAMA-0014,AutoMobil,Encéphalite avec autoanticorps anti-récepteurs synaptiques : un nouveau modèle de troubles psychotiques(2012), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre hospitalier Charles Perrens [Bordeaux], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris)
Subjects: Proband, Obsessive-Compulsive Disorder, Autism Spectrum Disorder, phenotype, Population, heritability, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Cognition, Intellectual disability, mental disorders, medicine, Humans, 0501 psychology and cognitive sciences, Expressivity (genetics), education, habits, Genetics (clinical), education.field_of_study, neurodevelopment, business.industry, General Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, Family aggregation, medicine.disease, Autism spectrum disorder, Autism, Neurology (clinical), business, 030217 neurology & neurosurgery, 050104 developmental & child psychology, Clinical psychology
Abstract: International audience; Repetitive behaviors (RB) represent a wide spectrum of symptoms ranging from sensory-motor stereotypies to complex cognitive rituals, frequently dichotomized as low- and high-order sub-groups of symptoms. Even though these subgroups are considered as phenomenologically distinct in autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD), brain imaging and genetic studies suggest that they have common mechanisms and pathways. This discrepancy may be explained by the frequent intellectual disability reported in ASD, which blurs the RB expressivity. Given the high heritability of RB, that is, the diversity of symptoms expressed in the relatives are dependent on those expressed in their probands, we hypothesize that if RB expressed in ASD or OCD are two distinct entities, then the RB expressed in relatives will also reflect these two dimensions. We thus conduct a linear discriminant analysis on RB in both the relatives of probands with ASD and OCD and subjects from the general population (n = 1023). The discriminant analysis results in a classification of 81.1% of the controls (p
Published: 2021

27. Impact of original, B.1.1.7, and B.1.351/P.1 SARS-CoV-2 lineages on vaccine effectiveness of two doses of COVID-19 mRNA vaccines: Results from a nationwide case-control study in France

Author: Alexandra Septfons, Simon Galmiche, Daniel Lévy-Bruhl, Simon Cauchemez, Sylvie van der Werf, Rebecca Grant, Alexandra Rogoff, Alexandra Maurizot, Cassandre Von Platen, Laura Schaeffer, Faïza Omar, Vincent Enouf, Olivia Chény, Christophe David, Alexandra Mailles, Fabrice Carrat, Bruno Lina, Louise H Lefrancois, Tiffany Charmet, Arnaud Fontanet, Alexandre Gaymard, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Sorbonne Université (SU), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris], Caisse Nationale d'Assurance Maladie des Travailleurs salariés (CNAMTS), Ministère de l'économie et des finances, Ipsos, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), The study was funded by Institut Pasteur and Research & Action Emerging Infectious Diseases (REACTing). AF's laboratory receives support from the Labex IBEID (ANR-10-LABX-62-IBEID) and the INCEPTION project (PIA/ANR-16-CONV-0005) for studies on emerging viruses. TC is funded by the Fondation de France (Alliance 'Tous unis contre le virus'). SW's laboratory receives support from Institut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing (Research & Action Emerging Infectious Diseases), and by the H2020 project 101003589 (RECOVER)., We would like to thank the Action Coordonnée transmission group of the ANRS-MIE for helpful discussions on the study design, and Violette Mouro (Conseil d'Orientation de la Stratégie Vaccinale) for providing us with data on vaccine distribution in France., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Gestionnaire, HAL Sorbonne Université 5, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur)
Subjects: medicine.medical_specialty, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Lineage (evolution), case-control study, Biology, Virus, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, Internal Medicine, medicine, 030212 general & internal medicine, 030304 developmental biology, Vaccine effectiveness, 0303 health sciences, Messenger RNA, SARS-CoV-2 variants, Health Policy, Case-control study, COVID-19, Virology, Confidence interval, 3. Good health, Vaccination, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Public aspects of medicine, RA1-1270, Research Paper
Abstract: Background: We aimed to assess the effectiveness of two doses of mRNA COVID-19 vaccines against COVID-19 with the original virus and other lineages circulating in France. Methods: In this nationwide case-control study, cases were SARS-CoV-2 infected adults with onset of symptoms between 14 February and 3 May 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire on recent activity-related exposures and vaccination history. Information about the infecting virus was based on a screening RT-PCR for either B.1.1.7 or B.1.351/P.1 variants. Findings: Included in our analysis were 7 288 adults infected with the original SARS-CoV-2 virus, 31 313 with the B.1.1.7 lineage, 2 550 with B.1.351/P1 lineages, and 3 644 controls. In multivariable analysis, the vaccine effectiveness (95% confidence interval) seven days after the second dose of mRNA vaccine was estimated at 88% (81-92), 86% (81-90) and 77% (63-86) against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. Recent (2 to 6 months) history of virologically confirmed SARS-CoV-2 infection was found to be 83% (76-88), 88% (85-91) and 83% (71-90) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively; and more distant (> 6 months) infections were 76% (54-87), 84% (75-90), and 74% (41-89) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. Interpretation: In real-life settings, two doses of mRNA vaccines proved to be effective against COVID-19 with the original virus, B.1.1.7 lineage and B.1.351/P.1 lineages. Funding: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance “Tous unis contre le virus”).
Published: 2021

28. Procainamide-SAHA fused inhibitors of hHDAC6 tackle multi-drug resistant malaria parasites

Author: Elie Hammam, Roger Peronet, Artur Scherf, Salah Mecheri, Camille Roesch, Ludovic Halby, Corentin Bon, Irina Dobrescu, Ambre Tafit, Paola B. Arimondo, Aurélie Claes, Diane Erdmann, Johanna Viluma, Véronique Cadet-Daniel, Melissa Mairet-Khedim, Benoit Witkowski, Flore Nardella, Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chimie biologique épigénétique - Epigenetic Chemical Biology (EpiCBio), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Ecole doctorale Médicament -Toxicologie - Chimie - Imageries [Université de Paris] (ED 563), Université Paris Cité (UPCité), Malaria Molecular Epidemiology, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), This work was supported by the Innovation program by Institut Pasteur-Institut Carnot (S-CR18089-02B15 DARRI CONSO INNOV 46-19, S-PI15006-10A INNOV 05-2019 ARIMONDO IARP 2019-PC), Pasteur Transversal Research Program (PTR 233-2019 HALBY), Pasteur Swiss Foundation grant, and ANR AAPG 2020-EpiKillMal, ANR-20-CE18-0006,EpiKillMal,Cibler la méthylation de l'ADN pour contrer la chimiorésistance du paludisme(2020), Nardella, Flore, Cibler la méthylation de l'ADN pour contrer la chimiorésistance du paludisme - - EpiKillMal2020 - ANR-20-CE18-0006 - AAPG2020 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), and Malaria Molecular Epidemiology (MMEU)
Subjects: medicine.medical_treatment, DNA Methyltransferase Inhibitor, Parasitemia, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Pharmacology, Histone Deacetylase 6, Hydroxamic Acids, 01 natural sciences, HDAC6 inhibitors, Drug Discovery, Malaria, Falciparum, Cytotoxicity, 0303 health sciences, DNA methylation, antimalarial, Molecular Structure, biology, Chemistry, Drug Resistance, Multiple, 3. Good health, in vivo, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, parasite, Molecular Medicine, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Plasmodium falciparum, malaria, Dihydroartemisinin, Procainamide, Antimalarials, Structure-Activity Relationship, 03 medical and health sciences, parasitic diseases, medicine, Gametocyte, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Histone deacetylase, 030304 developmental biology, drug resistance, Dose-Response Relationship, Drug, biology.organism_classification, medicine.disease, 0104 chemical sciences, Histone Deacetylase Inhibitors, Multiple drug resistance, 010404 medicinal & biomolecular chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Malaria
Abstract: International audience; Epigenetic post-translational modifications are essential for human malaria parasite survival and progression through its life cycle. Here, we present new functionalized suberoylanilide hydroxamic acid (SAHA) derivatives that chemically combine the pan-histone deacetylase inhibitor SAHA with the DNA methyltransferase inhibitor procainamide. A three- or four-step chemical synthesis was designed starting from cheap raw materials. Compared to the single drugs, the combined molecules showed a superior activity in Plasmodium and a potent inhibition against human HDAC6, exerting no cytotoxicity in human cell lines. These new compounds are fully active in multidrug-resistant Plasmodium falciparum Cambodian isolates. They target transmission of the parasite by inducing irreversible morphological changes in gametocytes and inhibiting exflagellation. The compounds are slow-acting and have an additive antimalarial effect in combination with fast-acting epidrugs and dihydroartemisinin. The lead compound decreases parasitemia in mice in a severe malaria model. Taken together, this novel fused molecule offers an affordable alternative to current failing antimalarial therapy.
Published: 2021

29. Proteome remodeling in the Mycobacterium tuberculosis PknG knockout: Molecular evidence for the role of this kinase in cell envelope biogenesis and hypoxia response

Author: Wehenkel, Anne Marie, Lima, Analía, Leyva, Alejandro, Rivera, Bernardina, Portela, María Magdalena, Gil, Magdalena, Cascioferro, Alessandro, Lisa, María-Natalia, Wehenkel, Annemarie, Bellinzoni, Marco, Carvalho, Paulo, Batthyány, Carlos, Alvarez, María, Brosch, Roland, Alzari, Pedro, Durán, Rosario, Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), Instituto de Investigaciones Biológicas Clemente Estable [Montevideo] (IIBCE), Universidad de la República Uruguay, Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Instituto de Biología Molecular y Celular de Rosario [Rosario] (IBR), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Universidad Nacional de Rosario [Santa Fe], Fiocruz Paraná - Instituto Carlos Chagas / Carlos Chagas Institute [Curitiba, Brésil] (ICC), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Universidad de la República [Montevideo] (UCUR), This work was supported by grants from Agencia Nacional de Investigación e Innovación, Uruguay (ANII, FCE_3_2013_1_100358 and FCE_1_2014_1_104045) and FOCEM - Fondo para la Convergencia Estructural del Mercosur (COF 03/11). MG and BR were supported by fellowships from ANII [POS_NAC_2012_1_8824, POS_NAC_2015_1_109755, POS_FCE_2015_1_1005186]. AC and RB were supported by the Agence Nationale pour la Recherche (France)., Universidad de la República [Montevideo] (UDELAR), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ)
Subjects: 0301 basic medicine, Proteomics, Tuberculosis, Proteome, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Quantitative proteomics, Mutant, Biophysics, Serine threonine protein kinase, PknG, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Protein Serine-Threonine Kinases, Biochemistry, Mycobacterium tuberculosis, 03 medical and health sciences, Bacterial Proteins, medicine, [CHIM.CRIS]Chemical Sciences/Cristallography, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Hrp-1, Serine/Threonine protein kinase, Hypoxia, Protein kinase A, ComputingMilieux_MISCELLANEOUS, Biological Phenomena, 030304 developmental biology, Msl3, 0303 health sciences, 030102 biochemistry & molecular biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, 030306 microbiology, Kinase, medicine.disease, biology.organism_classification, 3. Good health, Cell biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, Mas, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Biogenesis, Intracellular
Abstract: International audience; Mycobacterium tuberculosis, the etiological agent of tuberculosis, is among the deadliest human pathogens. One of M. tuberculosis's pathogenic hallmarks is its ability to persist in a dormant state in the host. Thus, this pathogen has developed mechanisms to withstand stressful conditions found in the human host. Particularly, the Ser/Thr-protein kinase PknG has gained relevance since it regulates nitrogen metabolism and facilitates bacterial survival inside macrophages. Nevertheless, the molecular mechanisms underlying these effects are far from being elucidated. To further investigate these issues, we performed quantitative proteomic analyses of protein extracts from M. tuberculosis H37Rv and a mutant lacking pknG. We found that in the absence of PknG the mycobacterial proteome was remodeled since 5.7% of the proteins encoded by M. tuberculosis presented significant changes in its relative abundance compared with the wild-type. The main biological processes affected by pknG deletion were cell envelope components biosynthesis and response to hypoxia. Thirteen DosR-regulated proteins were underrepresented in the pknG deletion mutant, including Hrp-1, which was 12.5-fold decreased according to Parallel Reaction Monitoring experiments. Altogether, our results allow us to postulate that PknG regulation of bacterial adaptation to stress conditions might be an important mechanism underlying its reported effect on intracellular bacterial survival. SIGNIFICANCE: PknG is a Ser/Thr kinase from Mycobacterium tuberculosis with key roles in bacterial metabolism and bacterial survival within the host. However, at present the molecular mechanisms underlying these functions remain largely unknown. In this work, we evaluate the effect of pknG deletion on M. tuberculosis proteome using different approaches. Our results clearly show that the global proteome was remodeled in the absence of PknG and shed light on new molecular mechanism underlying PknG role. Altogether, this work contributes to a better understanding of the molecular bases of the adaptation of M. tuberculosis, one of the most deadly human pathogens, to its host.
Published: 2021

30. Genomic history of human monkey pox infections in the Central African Republic between 2001 and 2018

Author: Nicolas, Berthet, Stéphane, Descorps-Declère, Camille, Besombes, Manon, Curaudeau, Andriniaina Andy, Nkili Meyong, Benjamin, Selekon, Ingrid, Labouba, Ella Cyrielle, Gonofio, Rita Sem, Ouilibona, Huguette Dorine, Simo Tchetgna, Maxence, Feher, Arnaud, Fontanet, Mirdad, Kazanji, Jean-Claude, Manuguerra, Alexandre, Hassanin, Antoine, Gessain, Emmanuel, Nakoune, Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP), Cellule d'Intervention Biologique d'Urgence (Centre National de Référence) - Laboratory for Urgent Response to Biological Threats (National Reference Center) (CIBU), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), Centre International de Recherches Médicales de Franceville (CIRMF), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Institut Pasteur de Bangui, Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This study was supported by the CIRMF, which is supported by the Government of Gabon, the Ministère de la Coopération Française and Total-Fina-Elf Gabon. This project was also supported by Agence National de la Recherche (Grant AFRIPOX) and Fondation SCOR as well as the Chinese Academy of Sciences, a Shanghai Municipal Science and Technology Major Project (Grant No. 2019SHZDZX02), External Cooperation Program of Chinese Academy of Sciences (Grant no. 153211KYSB20160001)., We would like to acknowledge WHO teams, national and local health authorities and the Institut Pasteur Bangui teams for their active participation to field outbreak investigations. We acknowledge Dr. Carolyn Engel-Gautier for editing the English in the manuscript., ANR-19-CE35-0011,AFRIPOX,Etude 'One Health' sur le monkeypox: infection humaine, réservoir animal, écologie de la maladie et outils diagnostiques(2019), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Pox virus, Science, [SDV]Life Sciences [q-bio], Genomics, Monkeypox, Biological Evolution, Article, Central African Republic, Evolution, Molecular, Phylogenetics, Humans, Medicine, Monkeypox virus, Viral evolution, Phylogeny
Abstract: International audience; Monkeypox is an emerging infectious disease, which has a clinical presentation similar to smallpox. In the two past decades, Central Africa has seen an increase in the frequency of cases, with many monkeypox virus (MPXV) isolates detected in the Democratic Republic of Congo (DRC) and the Central African Republic (CAR). To date, no complete MPXV viral genome has been published from the human cases identified in the CAR. The objective of this study was to sequence the full genome of 10 MPXV isolates collected during the CAR epidemics between 2001 and 2018 in order to determine their phylogenetic relationships among MPXV lineages previously described in Central Africa and West Africa. Our phylogenetic results indicate that the 10 CAR isolates belong to three lineages closely related to those found in DRC. The phylogenetic pattern shows that all of them emerged in the rainforest block of the Congo Basin. Since most human index cases in CAR occurred at the northern edge of western and eastern rainforests, transmissions from wild animals living in the rainforest is the most probable hypothesis. In addition, molecular dating estimates suggest that periods of intense political instability resulting in population movements within the country often associated also with increased poverty may have led to more frequent contact with host wild animals. The CAR socio-economic situation, armed conflicts and ecological disturbances will likely incite populations to interact more and more with wild animals and thus increase the risk of zoonotic spillover.
Published: 2021

31. Single-molecule localization microscopy

Author: Markus Sauer, Florian Schueder, Melike Lakadamyali, Gerti Beliu, Melina Theoni Gyparaki, Suliana Manley, Ralf Jungmann, Juliette Griffié, Mickaël Lelek, Christophe Zimmer, Imagerie et Modélisation - Imaging and Modeling, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, University of Würzburg = Universität Würzburg, Ludwig Maximilian University [Munich] (LMU), Max-Planck-Institut für Biochemie = Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft, Ecole Polytechnique Fédérale de Lausanne (EPFL), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), C.Z. acknowledges funding by Institut Pasteur, Fondation pour la Recherche Médicale (grant DEQ 20150331762), Région Ile de France, Agence Nationale de la Recherche and Investissement d’Avenir grant ANR-16-CONV-0005. M.La. acknowledges funding from the National Institutes of Health/National Institutes of General Medical Sciences (NIH/NIGMS) under grant RO1 GM133842-01. G.B. and M.S. acknowledge funding by the German Research Foundation (DFG) (SA829/19-1) and the European Regional Development Fund (EFRE project ‘Center for Personalized Molecular Immunotherapy’). F.S. and R.J. acknowledge support by the DFG through SFB1032 (project A11) and the Max Planck Society. J.G. and S.M. acknowledge funding by the European Union’s H2020 programme under the Marie Skłodowska-Curie grant BALTIC (to J.G.) and ERC Piko (to S.M.)., The authors apologize to the authors of numerous papers that could not be cited owing to limited space. M.Le. and C.Z. thank B. Lelandais for excellent comments on the manuscript and M. Singh for acquiring the image shown in Fig. 3b., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania [Philadelphia], Max Planck Institute of Biochemistry (MPIB), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)
Subjects: Single molecule localization, light-microscopy, Computer science, business.industry, General Medicine, Article, General Biochemistry, Genetics and Molecular Biology, optical reconstruction microscopy, diffraction-limit, Fluorescent labelling, 3-dimensional superresolution, live-cell, correlative superresolution fluorescence, Microscopy, Time course, Image acquisition, colocalization analysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Computer vision, Artificial intelligence, business, living cells, intramolecular spirocyclization, Image resolution, electron-microscopy
Abstract: Single-molecule localization microscopy (SMLM) describes a family of powerful imaging techniques that dramatically improve spatial resolution over standard, diffraction-limited microscopy techniques and can image biological structures at the molecular scale. In SMLM, individual fluorescent molecules are computationally localized from diffraction-limited image sequences and the localizations are used to generate a super-resolution image or a time course of super-resolution images, or to define molecular trajectories. In this Primer, we introduce the basic principles of SMLM techniques before describing the main experimental considerations when performing SMLM, including fluorescent labelling, sample preparation, hardware requirements and image acquisition in fixed and live cells. We then explain how low-resolution image sequences are computationally processed to reconstruct super-resolution images and/or extract quantitative information, and highlight a selection of biological discoveries enabled by SMLM and closely related methods. We discuss some of the main limitations and potential artefacts of SMLM, as well as ways to alleviate them. Finally, we present an outlook on advanced techniques and promising new developments in the fast-evolving field of SMLM. We hope that this Primer will be a useful reference for both newcomers and practitioners of SMLM. This Primer explains the central concepts of single-molecule localization microscopy (SMLM) before discussing experimental considerations regarding fluorophores, optics and data acquisition, processing and analysis. The Primer further describes recent high-impact discoveries made by SMLM techniques and concludes by discussing emerging methodologies.
Published: 2021

32. Ser/Thr Kinase-Dependent Phosphorylation of the Peptidoglycan Hydrolase CwlA Controls Its Export and Modulates Cell Division in Clostridioides difficile

Author: Transito Garcia-Garcia, Sandrine Poncet, Elodie Cuenot, Thibaut Douché, Quentin Giai Gianetto, Johann Peltier, Pascal Courtin, Marie-Pierre Chapot-Chartier, Mariette Matondo, Bruno Dupuy, Thomas Candela, Isabelle Martin-Verstraete, Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateforme de Protéomique / Proteomics platform, Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), This work was funded by the Institut Pasteur, the Université de Paris, and grants from the ITN Marie Curie, Clospore (H2020-MSCA-ITN-2014 642068), and the ANR (ANR-17-CE15-0018-01). E.C. and T.G.G. are the recipients of an ITN Marie Curie and an ANR fellowship, respectively., The anti-Cwp66 antibody was a gift from N. Fairweather. This work has benefited from the facilities and expertise of Christine Longin and MIMA2 MET, INRA-UMR GABI., ANR-17-CE15-0018,DifKin,Une Ser/Thr kinase impliquée dans la résistance à des composés antimicrobiens importants pour la colonization chez Clostridium difficile(2017), European Project: 642068,H2020,H2020-MSCA-ITN-2014,CLOSPORE(2015), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: cell division, control of exportation, envelope homeostasis, Clostridioides difficile, phosphorylation, N-Acetylmuramoyl-L-alanine Amidase, Clostridium difficile, anaerobes, Protein Serine-Threonine Kinases, peptidoglycan, Microbiology, QR1-502, protein phosphorylation, kinases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Bacterial Proteins, Hanks kinase, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], cell wall, cell wall hydrolases, Research Article, Signal Transduction
Abstract: International audience; Cell growth and division require a balance between synthesis and hydrolysis of the peptidoglycan (PG). Inhibition of PG synthesis or uncontrolled PG hydrolysis can be lethal for the cells, making it imperative to control peptidoglycan hydrolase (PGH) activity. The synthesis or activity of several key enzymes along the PG biosynthetic pathway is controlled by the Hanks-type serine/threonine kinases (STKs). In Gram-positive bacteria, inactivation of genes encoding STKs is associated with a range of phenotypes, including cell division defects and changes in cell wall metabolism, but only a few kinase substrates and associated mechanisms have been identified. We previously demonstrated that STK-PrkC plays an important role in cell division, cell wall metabolism, and resistance to antimicrobial compounds in the human enteropathogen Clostridioides difficile . In this work, we characterized a PG hydrolase, CwlA, which belongs to the NlpC/P60 family of endopeptidases and hydrolyses cross-linked PG between daughter cells to allow cell separation. We identified CwlA as the first PrkC substrate in C. difficile . We demonstrated that PrkC-dependent phosphorylation inhibits CwlA export, thereby controlling hydrolytic activity in the cell wall. High levels of CwlA at the cell surface led to cell elongation, whereas low levels caused cell separation defects. Thus, we provided evidence that the STK signaling pathway regulates PGH homeostasis to precisely control PG hydrolysis during cell division. IMPORTANCE Bacterial cells are encased in a PG exoskeleton that helps to maintain cell shape and confers physical protection. To allow bacterial growth and cell separation, PG needs to be continuously remodeled by hydrolytic enzymes that cleave PG at critical sites. How these enzymes are regulated remains poorly understood. We identify a new PG hydrolase involved in cell division, CwlA, in the enteropathogen C. difficile . Lack or accumulation of CwlA at the bacterial surface is responsible for a division defect, while its accumulation in the absence of PrkC also increases susceptibility to antimicrobial compounds targeting the cell wall. CwlA is a substrate of the kinase PrkC in C. difficile . PrkC-dependent phosphorylation controls the export of CwlA, modulating its levels and, consequently, its activity in the cell wall. This work provides a novel regulatory mechanism by STK in tightly controlling protein export.
Published: 2021

33. Long-term outcome in neuroZika

Author: Quentin Lobjois, Pascale Poullain, Etienne C. Hirsch, Guillaume Thiery, Françoise Lazarini, Fatiha Najioullah, Jean-Louis Fergé, Emmanuel Roze, Sébastien Breurec, Anne-Charlotte Savidan, Benoit Tressières, Annie Lannuzel, Eavan McGovern, Aissatou Signate, André Cabié, Ruddy Valentino, Yoann Madec, Pierre-Marie Lledo, Benoît Rozé, Raymond Césaire, Cécile Herrmann, Hirsch, Etienne, Service de Neurologie [CHU Pointe à Pitre], CHU Pointe-à-Pitre/Abymes [Guadeloupe], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU de la Martinique [Fort de France], Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur de la Guadeloupe, Réseau International des Instituts Pasteur (RIIP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Perception et Mémoire - Perception and Memory, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université des Antilles (UA), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Institut Pasteur [Paris], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Perception et Mémoire / Perception and Memory, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, West Indies, medicine.medical_treatment, Guillain-Barre Syndrome, [SCCO]Cognitive science, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, Interquartile range, Epidemiology, medicine, Humans, Encephalitis, Viral, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030212 general & internal medicine, Child, Encephalomyelitis, Stroke, Aged, Mechanical ventilation, Guillain-Barre syndrome, Zika Virus Infection, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Infant, Odds ratio, Middle Aged, Prognosis, medicine.disease, Respiration, Artificial, Cranial Nerve Diseases, 3. Good health, Hospitalization, Treatment Outcome, Child, Preschool, RNA, Viral, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, 030217 neurology & neurosurgery, Encephalitis
Abstract: ObjectiveTo characterize the full spectrum, relative frequency, and prognosis of the neurologic manifestations in Zika virus (ZIKV) postnatal infection.MethodsWe conducted an observational study in consecutive ZIKV-infected patients presenting with neurologic manifestations during the French West Indies 2016 outbreak.ResultsEighty-seven patients, including 6 children, were enrolled. Ninety-five percent of all cases required hospitalization. Guillain-Barré syndrome was the most frequent manifestation (46.0%) followed by encephalitis or encephalomyelitis (20.7%), isolated single or multiple cranial nerve palsies (9.2%), other peripheral manifestations (6.9%), and stroke (1.1%). Fourteen patients (16.1%), including one child, developed a mixed disorder involving both the central and peripheral nervous system. Mechanical ventilation was required in 21 cases, all of whom had ZIKV RNA in at least one biological fluid. Two adult patients died due to neuroZika. Clinical follow-up (median 14 months; interquartile range, 13–17 months) was available for 76 patients. Residual disability (modified Rankin Scale score ≥2) was identified in 19 (25.0%) patients; in 6 cases (7.9%), disability was severe (modified Rankin Scale score ≥4). Among patients with ZIKV RNA detected in one biological fluid, the risk of residual disability or death was higher (odds ratio 9.19; confidence interval 1.12–75.22; p = 0.039).ConclusionsNeuroZika spectrum represents a heterogeneous group of clinical neurologic manifestations. During an outbreak, clinicians should consider neuroZika in patients presenting with cranial nerve palsies and a mixed neurologic disorder. Long-term sequelae are frequent in NeuroZika. ZIKV reverse-transcription PCR status at admission can inform prognosis and should therefore be taken into consideration in the management of hospitalized patients.
Published: 2019

34. Statistical analysis of post-translational modifications quantified by label-free proteomics across multiple biological conditions with R: illustration from SARS-CoV-2 infected cells

Author: Gianetto Quentin, Giai, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Plateforme de Protéomique / Proteomics platform, Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut de Chimie du CNRS (INC)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: [STAT.AP]Statistics [stat]/Applications [stat.AP], Label-free proteomics, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Statistics, Relative quantification, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Data quality control, Clustering, Post-translational modifications
Abstract: Protein post-translational modifications (PTMs) are essential elements of cellular communication. Their variations in abundance can affect cellular pathways, leading to cellular disorders and diseases. A widely used method for revealing PTM-mediated regulatory networks is their label-free quantitation (LFQ) by high-resolution mass spectrometry. The raw data resulting from such experiments are generally interpreted using specific software, such as MaxQuant, MassChroQ or Proline for instance. They provide data matrices containing quantified intensities for each modified peptide identified. Statistical analyses are then necessary (1) to ensure that the quantified data are of good enough quality and sufficiently reproducible, (2) to highlight the modified peptides that are differentially abundant between the biological conditions under study. The objective of this chapter is therefore to provide a complete data analysis pipeline for analyzing the quantified intensities of modified peptides in presence of two or more biological conditions using the R software. We illustrate our pipeline starting from MaxQuant outputs dealing with the analysis of A549-ACE2 cells infected by SARS-CoV-2 at different time stamps, freely available on PRIDE (PXD020019).
Published: 2021

35. Prevalence of SARS-CoV-2 antibodies in France: results from nationwide serological surveillance

Author: Louise Perrin de Facci, Virgile Monnet, Pierre Charneau, Caroline Demeret, Jean-Baptiste Richard, Nicolas Escriou, Daniel Lévy-Bruhl, Gabrielle Jones, Thierry Rose, François Anna, Yvonnick Guillois, Marion Gransagne, Corinne Robin, Sophie Goyard, Stéphane Petres, Stéphane Le Vu, Marie-Noëlle Ungeheuer, Lucie Léon, Laurent Filleul, Sylvie van der Werf, Sibylle Bernard-Stoecklin, Olivier Helynck, Harold Noel, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, Institut Pasteur [Paris], Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris]-TheraVectys, Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Chimie et Biocatalyse, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Laboratoire CERBA [Saint Ouen l'Aumône], Biomnis Sample Library (BSL), Eurofins Biomnis, Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), We thank Christine Larsen, Bruno Coignard and Jean-Claude Desenclos (Santé publiqueFrance) for their helpful contribution at setting up the study, from Institut Pasteur,Isabelle Cailleau for support in the funding process, Hélène Munier-Lehmann for accessto automate and supply management at the Unit of Chemistry and Biocatalysis, Yves L.Janin for providing the luciferase prosubstrate hikarazine 108, Philippe Souque forproduction of the lentiviral pseudo-types, the whole ICAReB team and COVID-19support staff for sample management at Institut Pasteur, Juliette Paireau (Institut Pas-teur, Santé publique France), Rodolphe Thiébaut (Bordeaux Université) and Xavier deLamballerie (Aix-Marseille Université) for valuable comments onfirst results. We alsothank the team from the Eurofins Biomnis Sample Library and from CerbaHealthcareBenedicte Roquebert (Laboratoire Cerba) and Marie Pierre Guerra (CerbaXpert) forcontributing to sample collection. Santé publique France provided funding to the NRCand to the two centralising biobanks to cover sample collection, preparation, transportand analysis costs. The funder had no role in analysis, interpretation of data or writing ofthe report. S.L.V., G.J. and H.N. had full access to all the data and had responsibility tosubmit for publication., Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-TheraVectys, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Lassailly-Bondaz, Anne, Santé publique France - French National Public Health Agency, Centre National de Référence des virus des infections respiratoires (dont la grippe) [Paris] (CNR), Santé publique France, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Male, Epidemiology, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Antibodies, Viral, Serology, 0302 clinical medicine, Seroepidemiologic Studies, Case fatality rate, Prevalence, Cumulative incidence, 030212 general & internal medicine, Child, Aged, 80 and over, 0303 health sciences, education.field_of_study, Multidisciplinary, biology, Transmission (medicine), Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Child, Preschool, Female, France, medicine.symptom, Antibody, Adult, medicine.medical_specialty, Adolescent, Science, Population, Asymptomatic, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Young Adult, medicine, Seroprevalence, Humans, education, Epidemics, 030304 developmental biology, Aged, business.industry, SARS-CoV-2, Public health, Infant, Newborn, COVID-19, Infant, General Chemistry, 030104 developmental biology, Viral infection, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Demography
Abstract: Assessment of the cumulative incidence of SARS-CoV-2 infections is critical for monitoring the course and extent of the COVID-19 epidemic. Here, we report estimated seroprevalence in the French population and the proportion of infected individuals who developed neutralising antibodies at three points throughout the first epidemic wave. Testing 11,000 residual specimens for anti-SARS-CoV-2 IgG and neutralising antibodies, we find nationwide seroprevalence of 0.41% (95% CI: 0.05–0.88) mid-March, 4.14% (95% CI: 3.31–4.99) mid-April and 4.93% (95% CI: 4.02–5.89) mid-May 2020. Approximately 70% of seropositive individuals have detectable neutralising antibodies. Infection fatality rate is 0.84% (95% CI: 0.70–1.03) and increases exponentially with age. These results confirm that the nationwide lockdown substantially curbed transmission and that the vast majority of the French population remained susceptible to SARS-CoV-2 in May 2020. Our study shows the progression of the first epidemic wave and provides a framework to inform the ongoing public health response as viral transmission continues globally., The percentage of national populations infected during the first stages of the COVID-19 pandemic are unclear owing to limited early testing. Here the authors provide a nation-wide prevalence study of SARS-CoV-2 antibodies in France from the first wave of COVID-19 in 2020, including stratification based on age, sex and region.
Published: 2021

36. High-risk exposure without personal protective equipment and infection with SARS-CoV-2 in healthcare workers: results of the CoV-CONTACT prospective cohort

Author: Yazdan Yazdanpanah, Patricia Bruijning-Verhagen, Charles Burdet, Xavier Duval, Jeremie Guedj, Thierry Rose, Sarah Tubiana, Sylvie van der Werf, Julia Bielicki, Pauline Manchon, François Blanquart, Sylvie Behillil, Loubna Alavoine, Diane Descamps, Anne Leclercq, Herman Goossens, Jean-Christophe Lucet, Mickael Attia, Michael Thy, Caroline Demeret, Charlotte Charpentier, N. Houhou, Bruno Lina, Centre d'Investigations Cliniques [CHU Bichat] (CIC plurithématique), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre de Ressources Biologiques [CHU Bichat], Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Hôpital Beaujon [AP-HP], Services de Maladies Infectieuses et Tropicales [CHU Bichat], Physique des fonctions biologiques / Physics of Biological Functions, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Infection and Immunity [Londres, UK], St George's, University of London, University Children’s Hospital Basel = Hôpital pédiatrique universitaire des deux Bâle [Bâle, Suisse] (UKBB), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Vaccine & Infectious Disease Institute [Antwerp, Belgium] (VAXINFECTIO), University of Antwerp (UA), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), The study was founded by Reacting, the French Ministry of Health (PHRC-N COVID-19, project PHRC-20-0242) and the European Commission (RECoVer, grant agreement 101003589). Some authors received financial support of the national research agency (ANR) through the ANR-Flash calls for COVID-19 (TheraCoV ANR-20-COVI-0018), ANR-20-COVI-0018,TheraCoV,Dynamique virale au niveau individuel et populationnel : implications pour l'optimisation des stratégies antivirales(2020), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], demeret, caroline, Dynamique virale au niveau individuel et populationnel : implications pour l'optimisation des stratégies antivirales - - TheraCoV2020 - ANR-20-COVI-0018 - COVID-19 - VALID, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, business.industry, SARS-CoV-2, healthcare workers, Risk of infection, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], 030231 tropical medicine, Pharmacist, transmission, 3. Good health, Serology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Health care, high-risk exposure, personal protective equipment, Medicine, 030212 general & internal medicine, Seroconversion, business, Prospective cohort study, Personal protective equipment
Abstract: ObjectiveWe aimed to estimate the risk of infection in Healthcare workers (HCWs) following a high-risk exposure without personal protective equipment (PPE).MethodsWe conducted a prospective cohort in HCWs who had a high-risk exposure to SARS-CoV-2-infected subject without PPE. Daily symptoms were self-reported for 30 days, nasopharyngeal swabs for SARS-CoV-2 RT-PCR were performed at inclusion and at days 3, 5, 7 and 12, SARS-CoV-2 serology was assessed at inclusion and at day 30. Confirmed infection was defined by positive RT-PCR or seroconversion, and possible infection by one general and one specific symptom for two consecutive days.ResultsBetween February 5thand May 30th, 2020, 154 HCWs were enrolled within 14 days following one high-risk exposure to either a hospital patient (70/154; 46.1%) and/or a colleague (95/154; 62.5%). At day 30, 25.0% had a confirmed infection (37/148; 95%CI, 18.4%; 32.9%), and 43.9% (65/148; 95%CI, 35.9%; 52.3%) had a confirmed or possible infection. Factors independently associated with confirmed or possible SARS-CoV-2 infection were being a pharmacist or administrative assistant rather than being from medical staff (adjusted OR (aOR)=3.8, CI95%=1.3;11.2, p=0.01), and exposure to a SARS-CoV-2-infected patient rather than exposure to a SARS-CoV-2-infected colleague (aOR=2.6, CI95%=1.2;5.9, p=0.02). Among the 26 HCWs with a SARS-CoV-2-positive nasopharyngeal swab, 7 (26.9%) had no symptom at the time of the RT-PCR positivity.ConclusionsThe proportion of HCWs with confirmed or possible SARS-CoV-2 infection was high. There were less occurrences of high-risk exposure with patients than with colleagues, but those were associated with an increased risk of infection.
Published: 2021

37. Potential role of the X circular code in the regulation of gene expression

Author: Christian J. Michel, Julie Dawn Thompson, Olivier Poch, Claudine Mayer, Raymond Ripp, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by Institute funds from the French Centre National de la Recherche Scientifique and the University of Strasbourg. This work was supported by French Infrastructure Institut Français de Bioinformatique (IFB) ANR-11-INBS-0013, and the ANR Grants Elixir-Excelerate: GA-676559 and RAinRARE: ANR-18-RAR3-0006-02., The authors would like to thank the BigEst and BICS Bioinformatics Platforms for their assistance., ANR-11-INBS-0013,IFB (ex Renabi-IFB),Institut français de bioinformatique(2011), ANR-18-RAR3-0006,RAinRARE(2018), European Project: 676559,H2020,H2020-INFRADEV-1-2015-1,ELIXIR-EXCELERATE(2015), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Paris Diderot, Equipe HAL, Infrastructures - Institut français de bioinformatique - - IFB (ex Renabi-IFB)2011 - ANR-11-INBS-0013 - INBS - VALID, ERA-NET E-RARE-3 - - RAinRARE2018 - ANR-18-RAR3-0006 - E-Rare-3 - VALID, ELIXIR-EXCELERATE: Fast-track ELIXIR implementation and drive early user exploitation across the life-sciences. - ELIXIR-EXCELERATE - - H20202015-09-01 - 2019-08-31 - 676559 - VALID, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Statistics and Probability, Reading Frames, Genetic code, [SDV]Life Sciences [q-bio], Computational biology, Biology, Genome, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Plasmid, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, [INFO]Computer Science [cs], Nucleotide Motifs, Codon, Gene, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Applied Mathematics, Circular code, Translation (biology), General Medicine, Ribosomal RNA, Codon optimization, Gene Expression Regulation, Modeling and Simulation, Codon usage bias, Transfer RNA, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Codon usage, Ribosomes, 030217 neurology & neurosurgery
Abstract: The X circular code is a set of 20 trinucleotides (codons) that has been identified in the protein-coding genes of most organisms (bacteria, archaea, eukaryotes, plasmids, viruses). It has been shown previously that the X circular code has the important mathematical property of being an error-correcting code. Thus, motifs of the X circular code, i.e. a series of codons belonging to X, which are significantly enriched in the genes, allow identification and maintenance of the reading frame in genes. X motifs have also been identified in many transfer RNA (tRNA) genes and in important functional regions of the ribosomal RNA (rRNA), notably in the peptidyl transferase center and the decoding center. Here, we investigate the potential role of X motifs as functional elements in the regulation of gene expression. Surprisingly, the definition of a simple parameter identifies several relations between the X circular code and gene expression. First, we identify a correlation between the 20 codons of the X circular code and the optimal codons/dicodons that have been shown to influence translation efficiency. Using previously published experimental data, we then demonstrate that the presence of X motifs in genes can be used to predict the level of gene expression. Based on these observations, we propose the hypothesis that the X motifs represent a new genetic signal, contributing to the maintenance of the correct reading frame and the optimization and regulation of gene expression.Author SummaryThe standard genetic code is used by (quasi-) all organisms to translate information in genes into proteins. Recently, other codes have been identified in genomes that increase the versatility of gene decoding. Here, we focus on the circular codes, an important class of genome codes, that have the ability to detect and maintain the reading frame during translation. Motifs of the X circular code are enriched in protein-coding genes from most organisms from bacteria to eukaryotes, as well as in important molecules in the gene translation machinery, including transfer RNA (tRNA) and ribosomal RNA (rRNA). Based on these observations, it has been proposed that the X circular code represents an ancestor of the standard genetic code, that was used in primordial systems to simultaneously decode a smaller set of amino acids and synchronize the reading frame. Using previously published experimental data, we highlight several links between the presence of X motifs in genes and more efficient gene expression, supporting the hypothesis that the X circular code still contributes to the complex dynamics of gene regulation in extant genomes.
Published: 2021

38. RNase R is associated in a functional complex with the RhpA DEAD-box RNA helicase in Helicobacter pylori

Author: Etienne Kornobis, Valérie Briolat, Maxime Bouilloux-Lafont, Cecília M. Arraiano, Bertrand Raynal, Eloïse Galtier, Mariette Matondo, Yves Quentin, Thibaut Douché, Alejandro Tejada-Arranz, Hilde De Reuse, Rute G. Matos, Pathogenèse de Helicobacter / Helicobacter Pathogenesis, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris (UP), Instituto de Tecnologia Química e Biológica António Xavier (ITQB), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Laboratoire de microbiologie et génétique moléculaires (LMGM), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Pôle Biomics (C2RT), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris]-Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Plateforme de Protéomique / Proteomics platform, Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biophysique Moléculaire (plateforme) - Molecular Biophysics (platform), European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie [665807], Institut Carnot Pasteur Microbes & Santé, Fondation pour la Recherche Médicale [DBF20161136767 to H.D.R.], Pasteur-Weizmann Consortium of ‘The Roles of Noncoding RNAs in Regulation of Microbial Life Styles and Virulence’ to HDR, work at ITQB NOVA was financially supported by: Project UIDB/04612/2020 and UIDP/04612/2020 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through FCT – Fundação para a Ciência e a Tecnologia, project PTDC/BIA-BQM/28479/2017 to R.G.M. R.G.M. was also financed by an FCT contract [CEECIND/02065/2017]. Funding for open access charge: Institut Pasteur., European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Laboratoire de microbiologie et génétique moléculaires - UMR5100 (LMGM), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Laboratoire de Microbiologie et de Génétique Moléculaires (LMGM) , Centre de Biologie Intégrative (CBI), Université de Toulouse, UMR CNRS 5100, 31062 TOULOUSE Cedex 9, France.
Subjects: DEAD box, AcademicSubjects/SCI00010, [SDV]Life Sciences [q-bio], Amino Acid Motifs, RNase R, DEAD-box RNA Helicases, 03 medical and health sciences, 5S ribosomal RNA, Exoribonuclease, Genetics, RNA, Double-Stranded, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Helicobacter pylori, biology, Nucleic Acid Enzymes, 030302 biochemistry & molecular biology, RNA, Ribosomal, 5S, Helicase, RNA, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], RNA Helicase A, Molecular biology, Exoribonucleases, biology.protein, Epsilonproteobacteria
Abstract: Ribonucleases are central players in post-transcriptional regulation, a major level of gene expression regulation in all cells. Here, we characterized the 3′-5′ exoribonuclease RNase R from the bacterial pathogen Helicobacter pylori. The ‘prototypical’ Escherichia coli RNase R displays both exoribonuclease and helicase activities, but whether this latter RNA unwinding function is a general feature of bacterial RNase R had not been addressed. We observed that H. pylori HpRNase R protein does not carry the domains responsible for helicase activity and accordingly the purified protein is unable to degrade in vitro RNA molecules with secondary structures. The lack of RNase R helicase domains is widespread among the Campylobacterota, which include Helicobacter and Campylobacter genera, and this loss occurred gradually during their evolution. An in vivo interaction between HpRNase R and RhpA, the sole DEAD-box RNA helicase of H. pylori was discovered. Purified RhpA facilitates the degradation of double stranded RNA by HpRNase R, showing that this complex is functional. HpRNase R has a minor role in 5S rRNA maturation and few targets in H. pylori, all included in the RhpA regulon. We concluded that during evolution, HpRNase R has co-opted the RhpA helicase to compensate for its lack of helicase activity.
Published: 2021

39. SARS-CoV-2 infection in schools in a northern French city: a retrospective serological cohort study in an area of high transmission, France, January to April 2020

Author: Ludivine Grzelak, Charlotte Renaudat, Yoann Madec, Lucie Kuhmel, Laurence Arowas, Caroline Demeret, Kuang-Yu Chen, Christèle Huon, Marie Noelle Ungeheuer, Marc Eloit, Olivier Schwartz, Thomas Bigot, Bernadette Crescenzo-Chaigne, Sandrine Fernandes Pellerin, Arnaud Fontanet, Isabelle Staropoli, Bruno Hoen, Nathalie Jolly, Camille Besombes, Sandie Munier, Isabelle Cailleau, Timothée Bruel, Pierre Charneau, Laura Tondeur, Sarah Temmam, Blanca Liliana Perlaza, Rebecca Grant, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Virus et Immunité - Virus and immunity, Université de Paris (UP), Direction de la recherche médicale de l'Institut Pasteur, Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Centre Médical de l'Institut Pasteur, Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biologie des ARN et virus influenza - RNA Biology of Influenza Virus, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris]-TheraVectys, Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, École nationale vétérinaire d'Alfort (ENVA), The study was funded by Institut Pasteur, and several laboratories participating in the study receive funding from the Labex IBEID (ANR-10-LABX-62-IBEID), REACTing and the INCEPTION project (PIA/ANR-16-CONV-0005) for studies focusing on emerging viruses. OS lab is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro- Immuno' ANR-14-CE14-0015-01 and the Gilead HIV cure program. LG is supported by the French Ministry of Higher Education, Research and Innovation. ME lab is funded by Institut Pasteur, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing (Research & Action Emerging Infectious Diseases), EU Grant 101003589 RECoVER., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Université Paris Cité (UPCité), Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École nationale vétérinaire - Alfort (ENVA), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut Pasteur [Paris] (IP)-TheraVectys
Subjects: 0301 basic medicine, Emerging infectious diseases, medicine.medical_specialty, MESH: Schools, Epidemiology, [SDV]Life Sciences [q-bio], Context (language use), Asymptomatic, Serology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Virology, MESH: Child, Humans, Medicine, MESH: COVID-19, MESH: SARS-CoV-2, 030212 general & internal medicine, Child, MESH: Cohort Studies, Retrospective Studies, Schools, MESH: Humans, Transmission (medicine), business.industry, SARS-CoV-2, Research, 4. Education, Public Health, Environmental and Occupational Health, COVID-19, Outbreak, Retrospective cohort study, MESH: Retrospective Studies, 3. Good health, Coronavirus disease 2019 (COVID-19), MESH: France, 030104 developmental biology, France, medicine.symptom, business, Demography, Cohort study
Abstract: Background Children’s role in SARS-CoV-2 epidemiology remains unclear. We investigated an initially unnoticed SARS-CoV-2 outbreak linked to schools in northern France, beginning as early as mid-January 2020. Aims This retrospective observational study documents the extent of SARS-CoV-2 transmission, linked to an affected high school (n = 664 participants) and primary schools (n = 1,340 study participants), in the context of unsuspected SARS-CoV-2 circulation and limited control measures. Methods Between 30 March and 30 April 2020, all school staff, as well as pupils and their parents and relatives were invited for SARS-CoV-2 antibody testing and to complete a questionnaire covering symptom history since 13 January 2020. Results In the high school, infection attack rates were 38.1% (91/239), 43.4% (23/53), and 59.3% (16/27), in pupils, teachers, and non-teaching staff respectively vs 10.1% (23/228) and 12.0% (14/117) in the pupils’ parents and relatives (p Conclusions Viral circulation can occur in high and primary schools so keeping them open requires consideration of appropriate control measures and enhanced surveillance.
Published: 2021

40. Genomic insights into population history and biological adaptation in Oceania

Author: Maximilian Larena, Guillaume Laval, Olivier Cassar, Lara R. Arauna, Lluis Quintana-Murci, Anne Boland, Mattias Jakobsson, Christine Harmant, Jean-François Deleuze, Frédérique Valentin, Mark Stoneking, Antoine Gessain, Albert Min-Shan Ko, Romain Laurent, Jeremy Choin, Laurent Excoffier, Robert Olaso, Javier Mendoza-Revilla, Paul Verdu, Sebastian Cuadros-Espinoza, Etienne Patin, Ying-Chin Ko, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Éco-Anthropologie (EAE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Archéologies et Sciences de l'Antiquité (ArScAn), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Uppsala University, Chinese Academy of Sciences [Beijing] (CAS), Éco-Anthropologie (EA), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris-Saclay, Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Ethnologie préhistorique, Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Environment-Omics-Disease Research Center, China Medical University and Hospital, Taichung, Taiwan, Institute of Ecology and Evolution [Bern, Switzerland], University of Bern, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Max Planck Institute for Evolutionary Anthropology [Leipzig], Max-Planck-Gesellschaft, Collège de France - Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), Pasteur-Roux-Cantarini fellowship, Collège de France, Fondation Allianz-Institut de France, CNRS, Ecole Doctorale 474 - FIRE-CRI-Programme Bettencourt, ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne (UNIL), Chaire Génomique humaine et évolution, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), and Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Neanderthal, Native Hawaiian or Other Pacific Islander, Human Migration, [SDV]Life Sciences [q-bio], Population, Oceania, Adaptation, Biological, Taiwan, Population genetics, Datasets as Topic, Genetic Introgression, Evolutionary genetics, 03 medical and health sciences, 0302 clinical medicine, biology.animal, Animals, Humans, Genetic variation, education, Denisovan, History, Ancient, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Neanderthals, Islands, 0303 health sciences, education.field_of_study, Multidisciplinary, Natural selection, Pacific Ocean, biology, Human evolutionary genetics, Asia, Eastern, Genome, Human, Australia, population genetics, Genomics, biology.organism_classification, Biological Evolution, Genetics, Population, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Evolutionary biology, Anthropology, Biological dispersal, 570 Life sciences, Adaptation, 030217 neurology & neurosurgery
Abstract: International audience; The Pacific region is of major importance for addressing questions regarding human dispersals, interactions with archaic hominins and natural selection processes1. However, the demographic and adaptive history of Oceanian populations remains largely uncharacterized. Here we report high-coverage genomes of 317 individuals from 20 populations from the Pacific region. We find that the ancestors of Papuan-related ('Near Oceanian') groups underwent a strong bottleneck before the settlement of the region, and separated around 20,000-40,000 years ago. We infer that the East Asian ancestors of Pacific populations may have diverged from Taiwanese Indigenous peoples before the Neolithic expansion, which is thought to have started from Taiwan around 5,000 years ago2-4. Additionally, this dispersal was not followed by an immediate, single admixture event with Near Oceanian populations, but involved recurrent episodes of genetic interactions. Our analyses reveal marked differences in the proportion and nature of Denisovan heritage among Pacific groups, suggesting that independent interbreeding with highly structured archaic populations occurred. Furthermore, whereas introgression of Neanderthal genetic information facilitated the adaptation of modern humans related to multiple phenotypes (for example, metabolism, pigmentation and neuronal development), Denisovan introgression was primarily beneficial for immune-related functions. Finally, we report evidence of selective sweeps and polygenic adaptation associated with pathogen exposure and lipid metabolism in the Pacific region, increasing our understanding of the mechanisms of biological adaptation to island environments.
Published: 2021

41. Prior infection by seasonal coronaviruses, as assessed by serology, does not prevent SARS-CoV-2 infection and disease in children, France, April to June 2020

Author: Marina Charbit, Johanne Auriau, Dulanjalee Kariyawasam, Isabelle Sermet-Gaudelus, Marc Eloit, Elsa Foucaud, Christèle Huon, Albert Faye, Delphine Chrétien, Flora Donati, Tiffany Guilleminot, Vincent Enouf, Bettina Mesplees, Coralie Briand, Marianne Leruez-Ville, Mélodie Aubart, Thomas Bigot, Sylvie van der Werf, Sarah Temmam, Brigitte Bader-Meunier, Mélanie Albert, Célia Crétolle, Agnès Delaunay-Moisan, Gilles Orliaguet, Grégoire Benoist, Vincent Gajdos, L. Fertitta, Bénédicte Pigneur, Julie Toubiana, Thibaut Lurier, Sylvie Behillil, Marija Backovic, Mathie Lorrot, marc duval-arnould, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris] (IP), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP - Hôpital Antoine Béclère [Clamart], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Rongeurs Sauvages, Risques Sanitaires et Gestion des Populations - UR 1233 (RS2GP), Virologie Structurale - Structural Virology, Département Plateforme (PF I2BC), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Hôpital Jean Verdier [AP-HP], Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Ambroise Paré [AP-HP], Hôpital Robert Debré Paris, Hôpital Robert Debré, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), Pasteur International Bioresources network (PIBNet), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École nationale vétérinaire - Alfort (ENVA), This work was supported by the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur., Martel, Anne-Sophie, UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and École nationale vétérinaire d'Alfort (ENVA)
Subjects: 0301 basic medicine, Male, Epidemiology, Cross-sectional study, viruses, [SDV]Life Sciences [q-bio], Disease, medicine.disease_cause, Antibodies, Viral, Serology, Coronavirus OC43, Human, 0302 clinical medicine, 030212 general & internal medicine, Child, skin and connective tissue diseases, Coronavirus, biology, virus diseases, OC43, Systemic Inflammatory Response Syndrome, 3. Good health, [SDV] Life Sciences [q-bio], Child, Preschool, Spike Glycoprotein, Coronavirus, Female, France, Seasons, Antibody, medicine.symptom, HKU1, Paris, Adolescent, Asymptomatic, 03 medical and health sciences, Immunity, Virology, medicine, Humans, Serologic Tests, 229E, business.industry, SARS-CoV-2, Research, Public Health, Environmental and Occupational Health, Infant, Newborn, Infant, COVID-19, medicine.disease, Systemic inflammatory response syndrome, 030104 developmental biology, Cross-Sectional Studies, NL63, biology.protein, business
Abstract: Background Children have a low rate of COVID-19 and secondary severe multisystem inflammatory syndrome (MIS) but present a high prevalence of symptomatic seasonal coronavirus infections. Aim We tested if prior infections by seasonal coronaviruses (HCoV) NL63, HKU1, 229E or OC43 as assessed by serology, provide cross-protective immunity against SARS-CoV-2 infection. Methods We set a cross-sectional observational multicentric study in pauci- or asymptomatic children hospitalised in Paris during the first wave for reasons other than COVID (hospitalised children (HOS), n = 739) plus children presenting with MIS (n = 36). SARS-CoV-2 antibodies directed against the nucleoprotein (N) and S1 and S2 domains of the spike (S) proteins were monitored by an in-house luciferase immunoprecipitation system assay. We randomly selected 69 SARS-CoV-2-seropositive patients (including 15 with MIS) and 115 matched SARS-CoV-2-seronegative patients (controls (CTL)). We measured antibodies against SARS-CoV-2 and HCoV as evidence for prior corresponding infections and assessed if SARS-CoV-2 prevalence of infection and levels of antibody responses were shaped by prior seasonal coronavirus infections. Results Prevalence of HCoV infections were similar in HOS, MIS and CTL groups. Antibody levels against HCoV were not significantly different in the three groups and were not related to the level of SARS-CoV-2 antibodies in the HOS and MIS groups. SARS-CoV-2 antibody profiles were different between HOS and MIS children. Conclusion Prior infection by seasonal coronaviruses, as assessed by serology, does not interfere with SARS-CoV-2 infection and related MIS in children.
Published: 2021

42. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies

Author: Samira Fafi-Kremer, Maaran Michael Rajah, Julian Buchrieser, Flora Donati, Thierry Prazuck, Mélanie Albert, Hugo Mouquet, Florence Guivel-Benhassine, Sylvie van der Werf, Aymeric Sève, Etienne Simon-Loriere, Laurent Hocqueloux, Françoise Porrot, Emmanuelle Varon, Hélène Péré, Karl Stefic, Vincent Enouf, Frédérique Schortgen, Layla Yahyaoui, Olivier Schwartz, Sylvie Behillil, Marianne Maquart, David Veyer, María González, Delphine Planas, Jérôme De Seze, Isabelle Staropoli, Elodie Bishop, Timothée Bruel, Matthieu Prot, Mounira Smati-Lafarge, Ludivine Grzelak, Cyril Planchais, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal de Créteil (CHIC), CHU Strasbourg, CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional d'Orléans (CHRO), Université de Strasbourg (UNISTRA), Centre National de Référence du VIH [Tours] (CNR VIH), Work in the laboratory of O.S. is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash COVID PROTEO-SARS-CoV-2 and IDISCOVR. Work in UPBI is funded by grant ANR-10-INSB-04-01 and Région Ile-de-France program DIM1-Health. D.P. is supported by the Vaccine Research Institute. L.G. is supported by the French Ministry of Higher Education, Research and Innovation. The laboratory of H.M. is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), the INSERM, REACTing and EU (RECOVER) grants. The laboratory of S.v.d.W. is funded by Institut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, EU grant RECOVER. The laboratory of S.F.-K. is funded by Strasbourg University Hospital (SeroCoV-HUS, PRI 7782), Programme Hospitalier de Recherche Clinique (PHRC N 2017-HUS no. 6997), the Agence Nationale de la Recherche (ANR-18-CE17-0028), Laboratoire d’Excellence TRANSPLANTEX (ANR-11-LABX-0070_TRANSPLANTEX) and Institut National de la Santé et de la Recherche Médicale (UMR_S 1109). Work in CHR Orléans is funded by COREVIH Centre Val de Loire., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-18-CE17-0028,HuMABK,Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées(2018), ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Donati, Flora, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées - - HuMABK2018 - ANR-18-CE17-0028 - AAPG2018 - VALID, Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app - - TRANSPLANTEX2011 - ANR-11-LABX-0070 - LABX - VALID, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), and Centre National de Référence du VIH [Tours] - laboratoire associé (CNR VIH)
Subjects: 0301 basic medicine, COVID-19 Vaccines, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Cross Reactions, Antibodies, Viral, Sensitivity and Specificity, General Biochemistry, Genetics and Molecular Biology, Neutralization, Virus, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Immune system, Neutralization Tests, Humans, Medicine, media_common, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology, medicine.diagnostic_test, SARS-CoV-2, business.industry, Convalescence, Vaccination, COVID-19, General Medicine, Antibodies, Neutralizing, Virology, 3. Good health, [SDV] Life Sciences [q-bio], Titer, 030104 developmental biology, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Antibody, business
Abstract: International audience; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 and B.1.351 variants were first identified in the United Kingdom and South Africa, respectively, and have since spread to many countries. These variants harboring diverse mutations in the gene encoding the spike protein raise important concerns about their immune evasion potential. Here, we isolated infectious B.1.1.7 and B.1.351 strains from acutely infected individuals. We examined sensitivity of the two variants to SARS-CoV-2 antibodies present in sera and nasal swabs from individuals infected with previously circulating strains or who were recently vaccinated, in comparison with a D614G reference virus. We utilized a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection. Sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. In contrast, after 9 months, convalescent sera had a mean sixfold reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Sera from 19 individuals vaccinated twice with Pfizer Cominarty, longitudinally tested up to 6 weeks after vaccination, were similarly potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Neutralizing titers increased after the second vaccine dose, but remained 14-fold lower against B.1.351. In contrast, sera from convalescent or vaccinated individuals similarly bound the three spike proteins in a flow cytometry-based serological assay. Neutralizing antibodies were rarely detected in nasal swabs from vaccinees. Thus, faster-spreading SARS-CoV-2 variants acquired a partial resistance to neutralizing antibodies generated by natural infection or vaccination, which was most frequently detected in individuals with low antibody levels. Our results indicate that B1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.
Published: 2021

43. Early assessment of diffusion and possible expansion of SARS-CoV-2 Lineage 20I/501Y.V1 (B.1.1.7, variant of concern 202012/01) in France, January to March 2021

Author: Gaymard, Alexandre, Bosetti, Paolo, Feri, Adeline, Destras, Gregory, Enouf, Vincent, Andronico, Alessio, Burrel, Sonia, Behillil, Sylvie, Sauvage, Claire, Bal, Antonin, Morfin, Florence, Van Der Werf, Sylvie, Josset, Laurence, Blanquart, François, Coignard, Bruno, Cauchemez, Simon, Lina, Bruno, Gault, Elyanne, Moreau, Frédérique, Brichler, Ségolène, Delagrèverie, Héloïse, Descamps, Diane, Charpentier, Charlotte, Rozenberg, Flore, L'Honneur, Anne-Sophie, Veyer, David, Bélec, Laurent, Fourati, Slim, Rodriguez, Christophe, Pawlotsky, Jean-Michel, Fourgeaud, Jacques, Abid, Hanène, Roque-Afonso, Anne-Marie, Fenaux, Honorine, Jary, Aude, Marot, Stéphane, Salmona, Maud, Chaix, Marie-Laure, Morand-Joubert, Laurence, Schnuriger, Aurélie, Juillet, Stéphanie Marque, Bargain, Pauline, Poggi, Cécile, Chollet, Lionel, Guillaume, Clémence, Guinard, Jérôme, Vallet, Sophie, Pilorgé, Léa, Schvoerer, Evelyne, Hartard, Cédric, Castelain, Sandrine, François, Catherine, Ducancelle, Alexandra, Lefeuvre, Caroline, Lepiller, Quentin, Marty-Quinternet, Solène, Bellecave, Pantxika, Tumiotto, Camille, Dina, Julia, Le Gouil, Meriadeg, Henquell, Cécile, Mirand, Audrey, Césaire, Raymond, de Rougemont, Alexis, Auvray, Christelle, Larrat, Sylvie, Némoz, Benjamin, Tinez, Claire, Guigon, Aurélie, Hantz, Sébastien, Rogez, Sylvie, Dos Santos, Georges, Perez, Pascale, Jost, Christelle, Montes, Brigitte, Foulongne, Vincent, Imbert, Berthe-Marie, Bressollette, Céline, Giordanengo, Valérie, Gonfrier, Géraldine, Garcia, Magali, Lévêque, Nicolas, Brodard, Véronique, Moret, Hélène, Thibault, Vincent, Maillard, Anne, Jaffar-Bandjee, Marie-Christine, Gueudin, Marie, Plantier, Jean-Christophe, Pozzetto, Bruno, Pillet, Sylvie, Fafi-Kremer, Samira, Solis, Morgane, Izopet, Jacques, Trémeaux, Pauline, Stefic, Karl, Handala, Lynda, Billaud, Geneviève, Frobert, Emilie, Mérens, Audrey, Bigaillon, Christine, Desroches, Marine, Thepenier, Cédric, Janvier, Frédéric, Otto, Marie-Pierre, Roquebert, Bénédicte, Haïm-Boukobza, Stéphanie, Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Direction des maladies infectieuses - Infectious Diseases Division [Saint-Maurice], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Laboratoire de Virologie [CHU Amiens], CHU Amiens-Picardie, ANRS - Maladies infectieuses émergentes (ANRS - MIE), Institut National de la Santé et de la Recherche Médicale (INSERM), We acknowledge financial support from Santé publique France (the French national public health agency), the French Ministry of health (Grant COVIDseq), the Consortium for the surveillance and research on emerging pathogens via microbial genomics (EMERGEN) coordinated by Santé publique France and ANRS Maladies Infectieuses Emergentes, the Investissement d’Avenir programme, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases programme (grant ANR-10-LABX-62-IBEID), the European Union’s Horizon 2020 research and in-novation programme under grants 101003589 (RECOVER). This work has been supported by the laboratories belonging to the ColVHB network*., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Gestionnaire, Hal Sorbonne Université, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris)
Subjects: Author's Correction, Paris, medicine.medical_specialty, 2019-20 coronavirus outbreak, Lineage (genetic), Coronavirus disease 2019 (COVID-19), Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viral infections, [SDV]Life Sciences [q-bio], Context (language use), Biology, 03 medical and health sciences, 0302 clinical medicine, Virology, medicine, Humans, MESH: COVID-19, MESH: SARS-CoV-2, 030212 general & internal medicine, 030304 developmental biology, COVID, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, SARS-CoV-2, MESH: Paris, Public Health, Environmental and Occupational Health, COVID-19, [SDV] Life Sciences [q-bio], MESH: France, 20I/501Y.V1, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, surveillance, France, mutation, Rapid Communication, Demography
Abstract: International audience; The emergence of SARS-CoV-2 variant 20I/501Y.V1 (VOC-202012/1 or GR/501Y.V1) is concerning given its increased transmissibility. We reanalysed 11,916 PCR-positive tests (41% of all positive tests) performed on 7-8 January 2021 in France. The prevalence of 20I/501Y.V1 was 3.3% among positive tests nationwide and 6.9% in the Paris region. Analysing the recent rise in the prevalence of 20I/501Y.V1, we estimate that, in the French context, 20I/501Y.V1 is 52-69% more transmissible than the previously circulating lineages, depending on modelling assumptions.
Published: 2021

44. Queuine Is a Nutritional Regulator of Entamoeba histolytica Response to Oxidative Stress and a Virulence Attenuator

Author: Hajime Hisaeda, Shruti Nagaraja, Chikako Shimokawa, Samudrala Gourinath, Mohit Mazumdar, Hugo Varet, Rachel Legendre, Nancy Guillén, Maggi W. Cai, Serge Ankri, Thomas J. Begley, Peter C. Dedon, Jean-Yves Coppée, Lotem Sarid, Yana Shaulov, Yumiko Saito-Nakano, Jingjing Sun, Meirav Trebicz-Geffen, Technion - Israel Institute of Technology [Haifa], National University of Singapore (NUS), Singapore-MIT Alliance for Research and Technology (SMART), Massachusetts Institute of Technology (MIT), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris], Jawaharlal Nehru University (JNU), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Institute of Infectious Diseases, Shinjuku-ku, The work was supported by the Israel Ministry of Health within the framework European Research Area NETwork Infect-ERA (031L0004, AMOEBAC project), the Israel Science Foundation (260/16), the ISF-NRF program (3208/19), the National Research Foundation of Singapore through the Singapore-MIT Alliance for Research and Technology Antimicrobial Resistance IRG, the Rappaport Institute, the US–Israel Binational Science Foundation (2015211), and the Niedersachsen program., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Varet, Hugo
Subjects: TRNA modification, Guanine, [SDV]Life Sciences [q-bio], Queuosine, Virulence, Microbiology, Methylation, 03 medical and health sciences, chemistry.chemical_compound, Entamoeba histolytica, Mice, fluids and secretions, RNA, Transfer, Virology, parasitic diseases, Animals, Humans, Gene, 030304 developmental biology, 0303 health sciences, Mice, Inbred BALB C, biology, 030302 biochemistry & molecular biology, Queuine, Translation (biology), biology.organism_classification, QR1-502, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], virulence, Oxidative Stress, Biochemistry, chemistry, Transfer RNA, Female, tRNA modification, Research Article, HeLa Cells
Abstract: Entamoeba histolytica is a unicellular parasite that causes amebiasis. The parasite resides in the colon and feeds on the colonic microbiota., Queuosine is a naturally occurring modified ribonucleoside found in the first position of the anticodon of the transfer RNAs for Asp, Asn, His, and Tyr. Eukaryotes lack pathways to synthesize queuine, the nucleobase precursor to queuosine, and must obtain it from diet or gut microbiota. Here, we describe the effects of queuine on the physiology of the eukaryotic parasite Entamoeba histolytica, the causative agent of amebic dysentery. Queuine is efficiently incorporated into E. histolytica tRNAs by a tRNA-guanine transglycosylase (EhTGT) and this incorporation stimulates the methylation of C38 in tRNAGUCAsp. Queuine protects the parasite against oxidative stress (OS) and antagonizes the negative effect that oxidation has on translation by inducing the expression of genes involved in the OS response, such as heat shock protein 70 (Hsp70), antioxidant enzymes, and enzymes involved in DNA repair. On the other hand, queuine impairs E. histolytica virulence by downregulating the expression of genes previously associated with virulence, including cysteine proteases, cytoskeletal proteins, and small GTPases. Silencing of EhTGT prevents incorporation of queuine into tRNAs and strongly impairs methylation of C38 in tRNAGUCAsp, parasite growth, resistance to OS, and cytopathic activity. Overall, our data reveal that queuine plays a dual role in promoting OS resistance and reducing parasite virulence.
Published: 2021

45. Characterization of a highly neutralizing single monoclonal antibody to botulinum neurotoxin type A

Author: Christine Rasetti-Escargueil, Anne Wijkhuisen, Emmanuel Lemichez, Stéphanie Simon, Michel R. Popoff, Sébastien Brier, Maud Marechal, Plateforme technologique de RMN biologique - Biological NMR Technological Platform, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Toxines bactériennes - Bacterial Toxins, Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French joint ministerial program against CBRNE, ANR-11-EQPX-0008,CACSICE,Centre d'analyse de systèmes complexes dans les environnements complexes(2011), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: 0301 basic medicine, Gene isoform, medicine.drug_class, Protein Conformation, Nerve Tissue Proteins, Monoclonal antibody, Biochemistry, Epitope, Neutralization, 03 medical and health sciences, Epitopes, Mice, 0302 clinical medicine, Gangliosides, Genetics, medicine, Animals, Botulism, Botulinum Toxins, Type A, Molecular Biology, mass spectrometry, Antiserum, Membrane Glycoproteins, botulism, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Hydrogen-Deuterium eXchange, botulinum neurotoxin, synaptic vesicle protein 2, Antibodies, Monoclonal, medicine.disease, Molecular biology, Antibodies, Neutralizing, epitope mapping, 030104 developmental biology, Epitope mapping, Neuromuscular Agents, GT1b, monoclonal antibody, 030217 neurology & neurosurgery, Biotechnology, Conformational epitope
Abstract: International audience; Compared to conventional antisera strategies, monoclonal antibodies (mAbs) represent an alternative and safer way to treat botulism, a fatal flaccid paralysis due to botulinum neurotoxins (BoNTs). In addition, mAbs offer the advantage to be produced in a reproducible manner. We previously identified a unique and potent mouse mAb (TA12) targeting BoNT/A1 with high affinity and neutralizing activity. In this study, we characterized the molecular basis of TA12 neutralization by combining Hydrogen/Deuterium eXchange Mass Spectrometry (HDX-MS) with site-directed mutagenesis and functional studies. We found that TA12 recognizes a conformational epitope located at the interface between the HCN and HCC subdomains of the BoNT/A1 receptor-binding domain (HC ). The TA12-binding interface shares common structural features with the ciA-C2 VHH epitope and lies on the face opposite recognized by ciA-C2- and the CR1/CR2-neutralizing mAbs. The single substitution of N1006 was sufficient to affect TA12 binding to HC confirming the position of the epitope. We further uncovered that the TA12 epitope overlaps with the BoNT/A1-binding site for both the neuronal cell surface receptor synaptic vesicle glycoprotein 2 isoform C (SV2C) and the GT1b ganglioside. Hence, TA12 potently blocks the entry of BoNT/A1 into neurons by interfering simultaneously with the binding of SV2C and to a lower extent GT1b. Our study reveals the unique neutralization mechanism of TA12 and emphasizes on the potential of using single mAbs for the treatment of botulism type A.
Published: 2021

46. Nasopharyngeal and serological anti SARS-CoV-2 IgG/IgA responses in COVID-19 patients

Author: Sylvie van der Werf, Caroline Demeret, Bernadette Crescenzo-Chaigne, Lila Bouadma, Jade Ghosn, Vincent Enouf, Sarah Tubiana, Stéphane Petres, Marie Noelle Ungeheuer, Sylvie Behillil, Nicolas Escriou, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), Laboratoire d’innovation : vaccins – Innovation lab : vaccines, Plateforme technologique Production et purification de protéines recombinantes – Production and Purification of Recombinant Proteins Technological Platform (PPR), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigations Cliniques [CHU Bichat] (CIC plurithématique), This work was supported by the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur, by REACTING (Research & Action Emerging Infectious Diseases) and by the H2020 project 101003589 (RECOVER). The French Covid Cohort is funded through the Ministry of Health and Social Affairs (PHRC n°20-0424) and Ministry of Higher Education and Research dedicated COVID19 fund., List of the membership of the French COVID cohort study group : Mélanie RORIZ, Patrick RISPAL, Sarah REDL (CHG d'Agen), Laurent LEFEBVRE, Pascal GRANIER, Laurence MAULIN (CH du Pays d'Aix, Aix en Provence), Cédric JOSEPH, Julien MOYET, Sylvie LION-DAOLIO (CHU Amiens Nord), Rafael MAHIEU, Alexandra DU-CANCELLE, Vincent DUBEE (CHU d'Angers), Stéphane SALLA-BERRY, Aldric MANUEL, Gabriel MACHEDA, Mylène MAILLET, Bruno CHANZY (CH d'Annecy Genevois), Jean-Charles GAGNARD (Hôpital privé d'Antony), Guillermo GIORDANO, Clara MOUTON PERROT, Vincent PESTRE (CH Henri Duffaut, Avignon), Cécile FICKO, Marie GOMINET, Aurore BOUSQUET (Hôpital d'instruction des armées Begin), Charline VAUCHY, Kévin BOUILLER, Maïder PAGADOY, Solène MARTY-QUINTERNET, Quentin LEPILLER (CHU Jean Minjoz, Besançon), Cyril LE BRIS, Benoit THILL, Marie-Laure CASANOVA, Georges LE FALHER, Eric OZIOL (CH de Béziers), Hugues CORDEL, Nathalie DOURNON, Olivier BOUCHAUD, Ségolène BRICHLER (Hôpital Avicenne, Bobigny), Duc NGUYEN, Pantxika BELLECAVE, Camille CICCONE, Marie-Edith LAFON (CHU Pellegrin, Bordeaux), Ségolène GREFFE (CHU Ambroise Paré, Boulogne Billancourt), Camille BOUISSE, Nicholas SEDILLOT, Damien BOUHOUR (CH Fleyriat, Bourg en Bresse), Camille CHASSIN (CH Pierre Oudot, Bourgoin-Jallieu), Erwan L'HER, Séverine ANSART, Cécile TROMEUR, Dewi GUELLEC (CHRU de Brest), Antoine MERCKX (CH de Cahors), Felix DJOSSOU (CH Andrée Rosemon, Cayenne), Vincent PEIGNE, Carola PIEROBON, Marie-Christine CARRET, Florence JEGO, Margaux ISNARD (CHMS Chambéry NH), Johann AUCHABIE, Roxane COURTOIS (CH de Cholet), Olivier LESENS (CHU Gabriel Montpied, Clermont-Ferrand), Martin MARTINOT (Hôpital Pasteur, Colmar), Olivier PICONE (Hôpital Louis Mourier, Colombes), Marie LACOSTE (CH Alpes Leman Contamine sur Arve), Brigitte ELHAR-RAR, Valérie GARRAIT, Isabelle DELACROIX, Thomas MAITRE, Jean Baptiste ASSIE (Centre Hospitalier Intercommunal de Créteil), Elsa NYAMANKOLLY (CH de Dax), François Xavier CATHERINE, Ma-thieu BLOT, Sophie MAHY, Marielle BUISSON, Lionel PIROTH, Florence GUILLOTIN, Alexis DE ROUGEMONT (CHU de Dijon Bourgogne), Valentine CAMPANA, Jérémie PASQUIER, André CABIE (CHU de Martinique, Fort de France), Simon BESSIS (Hôpital Raymond Poincaré, Garches), Olivier EPAULARD, Nicolas TERZI, Jean-François PAYEN, Laurence BOUILLET, Rebecca HAMIDFAR, Marion Le MARECHAL (CHU de Grenoble), Moïse MACHADO, Audrey BARRELET, Alexandra BEDOSSA (Grand Hôpital de l'Est Francilien site Marne-la-Vallée, Jossigny), Gwenhaël COLIN, Romain DECOURS, Thomas GUIMARD (CHD Les Oudairies, La Roche Sur Yon), Cécile GOUJARD, Stéphane JAUREGUIBERRY, Antoine CHERET (Hôpital Universitaire Bicêtre, Le Kremlin-Bicêtre), Anne Sophie RESSEGUIER (CH Emile Roux, Le Puy en Velay), Julien POISSY, Daniel MATHIEU, Saad NSEIR, Ilka ENGELMANN, Martine REMY (CHRU de Lille, Hôpital Salengro), Fanny VUOTTO, Benoit GACHET, Karine FAURE, Marielle BOYER-BESSEYRE, Kazali Enagnon (CHRU de Lille, Hôpital Fourrier), Marc LAMBERT, Arnaud SCHERPEREEL, Dominique DEPLANQUE, Stéphanie FRY, Cécile YELNIK (CHRU de Lille, Hôpital Albert Calmette), Laurent BITKER, Mehdi MEZIDI, Hodane YONIS, Nicolas BENECH, Thomas PERPOINT, Anne CONRAD, Vinca ICARD, Martine VALETTE (Hôpital de la Croix Rousse, Lyon), Simon-Djamel THIBERVILLE (Hôpital Louis Raffalli, Manosque), Stanislas REBAUDET (Hôpital Européen de Marseille), Bertrand DUSSOL (Hôpital Conception, Marseille), Sylvain DIAMANTIS, Catherine CHAKVEATZE, Clara FLATEAU (Groupe Hospitalier Sud Ile De France, hôpital de Melun), Vincent DINOT, Rostane GACI, Nadia OUAMARA (Hôpital de Mercy, CHR Metz-Thionville, Ars laquenexy), Hajnal-Gabriela ILLES, Louis GER-BAUD MORLAES, Jérôme DIMET (CH de Mont Marsan), Vincent LE MOING, Nathalie PANSU, Clément LE BIHAN, Brigitte MONTES (CHU de Montpellier), Anne Sophie BOUREAU, Clotilde ALLAVENA, Sabelline BOUCHEZ, Romain GUERY, Paul LE TURNIER, Cécile MEAR-PASSARD, Virginie FERRE (CHU de Nantes), Christophe RAPP (Hôpital Américain de Paris, Neuilly sur Seine), Elisa DE-MONCHY, Céline MICHELANGELLI, Karine RISSO (CHU de Nice), Paul LOUBET, Jean-Phillippe LAVIGNE (CHU Caremeau, Nîmes), Etienne DE MONTMOLLIN, Juliette PATRIER, Paul Henri WICKY, Lucie LE FEVRE, Pierre JACQUET, Raphael BORIE, Antoine DOSSIER, Dominique LUTON, Valentina ISERNIA, Sylvie LE GAC (Hôpital Bichat, Paris), Cécile AZOULAY, Nicolas CARLIER, Liem LUONG, Marie LACHATRE, Odile LAUNAY (Hôpital Cochin, Paris), Younes KERROUMI, Vanina MEYSSONNIER (Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris), Jean-Luc DIEHL, Jean-Sébastien HULOT, Bernard CHOLLEY, Jean-Benoît ARLET, Olivier SANCHEZ (Hôpital Européen Georges Pompidou, Paris), Victoria MANDA, Laurène AZEMAR, Guylaine CASTOR-ALEXANDRE (Hôpital Lariboisière, Paris), Karine LACOMBE, Thibault CHIARABINI, Bénédicte LEFEBVRE, Laurence MORAND-JOUBERT, Djeneba FOFANA, Aurélie SCHNURIGER (Hôpital Saint Antoine, Paris), Nathalie DE CASTRO, Constance DELAUGERRE, Marie-Laure CHAIX (Hôpital Saint Louis, Paris), Julie CHAS (Hôpital Tenon, Paris), Valérie GABORIEAU, Eve LE COUSTUMIER, Walter PICARD (CH de Pau), Jean-Benoît ZABBE, Florent PEELMAN, Edouard SOUM (CH de Périgueux), Hugues AUMAÎTRE (CH de Perpignan), Elodie CURLIER, Rachida OUISSA, Isabelle FABRE (CHU de Pointe à Pitre, Guadeloupe), Blandine RAMMAERT (CHU de Poitiers), Nadia SAIDANI (CH Quimper), Firouzé BANI-SADR, Maxime HENTZIEN, Yohan N 'GUYEN, Juliette ROMARU, Kévin DIDIER (CHU Reims), Isabelle ENDERLE, Vincent THIBAULT, Fabrice LAINE, Matthieu LESOU-HAITIER, Matthieu REVEST, Pierre TATTEVIN (CHU Rennes), Jean-Christophe PLANTIER, Manuel ETIENNE, Véronique LEMEE, Eglantine FERRAND DEVOUGE, Kévin ALEXANDRE, Elise ARTAUD-MACCARI (CHU Rouen), Nathalie ALLOU, Marie LAGRANGE, Julien JABOT (CH Saint Denis et Saint Pierre, La réunion), Benoît ROZE, Delphine BREGEAUD, Younes AIT TAMLIHAT (CH Saintes), Ali HACHEMI (CH Soisson), Hélène SALVATOR, Erwan FOURN, David ZUCMAN (Hôpital Foch, Suresnes), Eric DELAVEUVE, Coline JAUD-FISCHER, Paul DUNAND (Hôpital Bel Air, Thionville), François BISSUEL (CH Thonon les Bains), Karen DELAVIGNE, Marie PIEL-JULIAN, Pierre DELOBEL, Benjamine SARTON, Marie RAFIQ, Guillaume MARTIN-BLONDEL, Laurent GUILLEMINAULT, Marlène MURRIS, Agnès SOMMET (CHU de Toulouse), Eric SENNEVILLE, Olivier ROBINEAU, Agnès MEYBECK (CH Tourcoing), Denis GAROT, Laurent PLANTIER, Valérie GISSOT, Julien MARLET, Karl STEFIC, Catherine GAUDY-GRAFFIN, Francis BARIN, Adrien LEMAIGNEN (CHU Bretonneau, Tours), Grégory CORVAISIER, Delphine LARIVIERE, Marie LANGELOT-RICHARD (CH Vannes), Elisabeth BOTELHO-NEVERS , Amandine GAGNEUX-BRUNON, Tiffany TROUILLON, Thomas BOURLET, Thomas BOURLET, Sylvie PILLET, Bruno POZZETTO (CHU de St Etienne), Antoine KIMMOUM, Bruno LEVY, Mathieu MATTEI, François GOEHRINGER, Christian RABAUD, Sibylle BEVILACQUA, Benjamin LEFEVRE, Anne GUILLAUMOT, Véronique VENARD, Hélène JEULIN, Evelyne SCHVOERER, Cédric HARTARD (CHU de Nancy, Vandoeuvre les Nancy), Pauline CARAUX PAZ, Laurent RICHIER, Mohamed EL SANHARAWI (CH Villeneuve St Georges)., European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord
Subjects: Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Severe disease, Infectious and parasitic diseases, RC109-216, Article, Serology, 03 medical and health sciences, 0302 clinical medicine, Medicine, Mucosal Immunity, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, business.industry, Epithelium, 3. Good health, Nucleoprotein, medicine.anatomical_structure, Antibody response, SARS CoV, 030220 oncology & carcinogenesis, Immunology, biology.protein, Antibody, business
Abstract: BackgroundThe systemic antibody responses to SARS-CoV-2 in COVID-19 patients has been extensively studied. However, much less is known about the mucosal responses in the upper airways at the site of initial SARS-CoV-2 replication. Local antibody responses in the nasopharyngeal epithelium, that are likely to determine the course of infection, have not been analysed so far nor their correlation with antibody responses in serum.MethodsThe IgG and IgA antibody responses were analysed in the plasma as well as in nasopharyngeal swabs (NPS) from the first four COVID-19 patients confirmed by RT-qPCR in France. Two were pauci-symptomatic while two developed severe disease. Taking advantage of a comprehensive series of plasma and nasopharyngeal samples, we characterized their antibody profiles from the second week post symptoms onset, by using an in-house ELISA to detect anti-SARS-CoV-2 Nucleoprotein (N) IgG and IgA.ResultsAnti-N IgG and IgA antibodies were detected in the NPS of severe patients. Overall, the levels of IgA and IgG antibodies in plasma and NPS appeared specific to each patient.ConclusionsAnti-N IgG and IgA antibodies are detected in NPS, and their levels are related to antibody levels in plasma. The two patients with severe disease exhibited different antibody profiles that may reflect different disease outcome. For the pauci-symptomatic patients, one showed a low anti-N IgG and IgA response in the plasma only, while the other one did not exhibit overt serological response.
Published: 2021

47. Cluster of COVID-19 in northern France: A retrospective closed cohort study

Author: Nathalie Jolly, Christèle Huon, Laura Tondeur, Bernadette Crescenzo, Sarah Temmam, Sandie Munier, Camille Besombes, Isabelle Staropoli, Timothée Bruel, Isabelle Cailleau, Rebecca Grant, Pierre Gallian, Simon Cauchemez, Marie-Noëlle Ungeheuer, Yoann Madec, Sylvie van der Werf, Bruno Hoen, Ludivine Grzelak, Marc Eloit, Sandrine Fernandes Pellerin, Olivier Schwartz, Caroline Demeret, Kuang-Yu Chen, Arnaud Fontanet, Lucie Kuhmel, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Sorbonne Université (SU), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Direction de la recherche médicale de l'Institut Pasteur, Centre Médical de l'Institut Pasteur (CMIP), Découverte de pathogènes – Pathogen discovery, Biologie des ARN et virus influenza - RNA Biology of Influenza Virus, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Université Paris Cité (UPCité), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, École nationale vétérinaire - Alfort (ENVA), Funding: Institut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, EU grant Recover, INCEPTION project (PIA/ANR-16-CONV-0005)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Virus et Immunité - Virus and immunity, Université de Paris (UP), École nationale vétérinaire d'Alfort (ENVA), demeret, caroline, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, Centre Médical de l'Institut Pasteur, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0303 health sciences, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, [SDV]Life Sciences [q-bio], Attack rate, Ageusia, Disease cluster, Confidence interval, 3. Good health, Herd immunity, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Internal medicine, Case fatality rate, medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, medicine.symptom, business, 030304 developmental biology, Cohort study
Abstract: SummaryBackgroundThe Oise department in France has been heavily affected by COVID-19 in early 2020.MethodsBetween 30 March and 4 April 2020, we conducted a retrospective closed cohort study among pupils, their parents and siblings, as well as teachers and non-teaching staff of a high-school located in Oise. Participants completed a questionnaire that covered history of fever and/or respiratory symptoms since 13 January 2020 and had blood tested for the presence of anti-SARS-CoV-2 antibodies. The infection attack rate (IAR) was defined as the proportion of participants with confirmed SARS-CoV-2 infection based on antibody detection. Blood samples from two blood donor centres collected between 23 and 27 March 2020 in the Oise department were also tested for presence of anti-SARS-CoV-2 antibodies.FindingsOf the 661 participants (median age: 37 years), 171 participants had anti-SARS-CoV-2 antibodies. The overall IAR was 25.9% (95% confidence interval (CI) = 22.6-29.4), and the infection fatality rate was 0% (one-sided 97.5% CI = 0 - 2.1). Nine of the ten participants hospitalised since mid-January were in the infected group, giving a hospitalisation rate of 5.3% (95% CI = 2.4 –9.8). Anosmia and ageusia had high positive predictive values for SARS-CoV-2 infection (84.7% and 88.1%, respectively). Smokers had a lower IAR compared to non-smokers (7.2% versus 28.0%, P InterpretationThe relatively low IAR observed in an area where SARS-CoV-2 actively circulated weeks before confinement measures indicates that establishing herd immunity will take time, and that lifting these measures in France will be long and complex.FundingInstitut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, EU grant Recover, INCEPTION project (PIA/ANR-16-CONV-0005).Research in contextEvidence before the studyThe first COVID-19 cases in France were reported on 24 January 2020. Substantial transmission has occurred since then, with the Oise department, north of Paris, one of the heaviest affected areas in the early stages of the epidemic in France. As of 13 April 2020, 98,076 cases had been diagnosed in France, including 5,379 deaths.Epidemiological and clinical characteristics of patients with COVID-19 have been widely reported, but this has largely been centred on cases requiring medical care. What remains unclear at this stage is the extent to which SARS-CoV-2 infections may be asymptomatic or present as subclinical, non-specific symptoms. While extensive contact tracing has identified asymptomatic infections using RT-PCR testing, serologic detection of anti-SARS-CoV-2 antibodies is needed to determine the real infection attack rate and the proportion of all infections that are asymptomatic or subclinical.Added value of this studyUsing a combination of serologic assays with high sensitivity and specificity for anti-SARS-CoV-2 antibodies, we conducted a retrospective closed cohort study. In a high school linked to a cluster of COVID-19 in the Oise department, we showed an overall infection attack rate (IAR) of 40.9% in the high school group, and 10.9% in parents and siblings of the pupils. The proportion of infected individuals who had no symptoms during the study period was 17.0%.Implications of all of the available evidenceThe relatively low IAR in this area where SARS-CoV-2 actively circulated before confinement measures were introduced indicates that establishing herd immunity will take time, and that the lifting of these measures in France will be long and complex.
Published: 2021

48. Mitochondrial respiration restricts Listeria monocytogenes infection by slowing down host cell receptor recycling

Author: Spier, Anna, Connor, Michael, Steiner, Thomas, Carvalho, Filipe, Cossart, Pascale, Eisenreich, Wolfgang, Wai, Timothy, Stavru, Fabrizia, Biologie Évolutive de la Cellule Microbienne - Evolutionary Biology of the Microbial Cell, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions Bactéries-Cellules, Institut Pasteur [Paris] (IP), Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Université Paris Cité (UPCité), Biologie mitochondriale – Mitochondrial biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This study was supported by the European Research Council ( H2020-ERC-2014-ADG 670823-BacCellEpi to P.C.), the DFG ( Project-ID EI 384/16-1 to W.E.), Institut Pasteur , and the Centre National de la Recherche Scientifique (CNRS). A.S. was supported by a BioSPC doctoral fellowship from the Université de Paris . M.G.C. is funded by a Pasteur Foundation Fellowship and his work was funded by ANR JCJC grant 'Epibactin.', We dedicate this work to the memory of Fabrizia Stavru. We thank Frédéric Bouillaud, Anne Lombès, and Nathalie Sauvonnet for useful advice, discussions, and support with Seahorse and endocytosis assays, Nam Tham for technical support, Werner Goebel for insightful discussions, Pierre-Henri Commere and members of the Cytometry & Biomarkers facility (CB_UTechS) at Institut Pasteur for training and help with flow cytometry and the Seahorse analyzer, and Alessandro Pagliuso and Simonetta Gribaldo for critical reading of the manuscript. Other bacterial species were GFP-expressing Salmonella enterica serovar Typhimurium strain 12023 (BUG2562) (a gift from Stéphane Méresse, Centre d’Immunologie de Marseille-Luminy, France) and Shigella flexneri M09T (BUG 2505) (a gift from Phillipe Sansonetti,Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris). We thank Dr. Matthew Lawrenz at the University of Louisville for sharing the Rab11bCA construct generated by M.G.C. while in his laboratory., ANR-17-CE12-0007,EpiBactIn,Modifications epigenomiques induites par l'interaction hote-bacteries(2017), European Project: 670823,H2020,ERC-2014-ADG,BacCellEpi(2015), Biologie Evolutive de la Cellule Microbienne - Evolutionary Biology of the Microbial Cell, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: [SDV]Life Sciences [q-bio], Respiration, Membrane Proteins, Proto-Oncogene Proteins c-met, HCT116 Cells, Listeria monocytogenes, infection, Mitochondria, endocytic recycling, Mitochondrial Proteins, mitochondrial disease, 13C isotopologue profiling, Report, Rab11, Colonic Neoplasms, Humans, Listeriosis, Energy Metabolism, metabolism, ComputingMilieux_MISCELLANEOUS
Abstract: Summary Mutations in mitochondrial genes impairing energy production cause mitochondrial diseases (MDs), and clinical studies have shown that MD patients are prone to bacterial infections. However, the relationship between mitochondrial (dys)function and infection remains largely unexplored, especially in epithelial cells, the first barrier to many pathogens. Here, we generate an epithelial cell model for one of the most common mitochondrial diseases, Leigh syndrome, by deleting surfeit locus protein 1 (SURF1), an assembly factor for respiratory chain complex IV. We use this genetic model and a complementary, nutrient-based approach to modulate mitochondrial respiration rates and show that impaired mitochondrial respiration favors entry of the human pathogen Listeria monocytogenes, a well-established bacterial infection model. Reversely, enhanced mitochondrial energy metabolism decreases infection efficiency. We further demonstrate that endocytic recycling is reduced in mitochondrial respiration-dependent cells, dampening L. monocytogenes infection by slowing the recycling of its host cell receptor c-Met, highlighting a previously undescribed role of mitochondrial respiration during infection., Graphical abstract, Highlights • Enhanced mitochondrial respiration decreases L. monocytogenes infection • Bacterial entry is affected by the host cell metabolism • Mitochondrial respiration restricts host cell receptor recycling and thus infection, Spier et al. show that the cellular energy metabolism affects infection of epithelial cells by L. monocytogenes. Mitochondrial respiration modulates L. monocytogenes entry by limiting endocytic recycling of receptors such as c-Met back to the plasma membrane, leading to decreased bacterial load in cells with high respiratory activity.
Published: 2021

49. Docosahexaenoic fatty acid-containing phospholipids affect plasma membrane susceptibility to disruption by bacterial toxin-induced macroapertures

Author: Frank Lafont, Jean-Christophe Olivo-Marin, Delphine Debayle, Amel Mettouchi, Emmanuel Lemichez, Lucile Fleuriot, David Gonzalez-Rodriguez, Meng-Chen Tsai, Bruno Antonny, Stephane Dallongeville, Camille Morel, Hélène Barelli, Sébastien Janel, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Toxines bactériennes - Bacterial Toxins, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes (LCP-A2MC), Université de Lorraine (UL), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Analyse d'images biologiques - Biological Image Analysis (BIA), This work was supported by a grant from the Fondation pour la Recherche Médicale (Convention DEQ20180339156 Equipes FRM 2018), the Agence Nationale de la Recherche (ANR-11-LABX-0028-01, ANR-15-CE18-0016,ANR10-EQPX-04-01, ANR-10-INBS-04, and ANR-10-LABX-62-IBEID) and FEDER 12,001,407. MCT was supported by a PhD fellowship from the Labex Signalife PhD Programme and by the Fondation pour la Recherche Médicale(Contrat FDT201904008135)., ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), ANR-15-CE18-0016,TransEndotheliaTunnel,Vers la prévention de dysfonctions vasculaires et la délivrance de médicaments au travers des endothelia(2015), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), DELARUE, NADINE, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Vers la prévention de dysfonctions vasculaires et la délivrance de médicaments au travers des endothelia - - TransEndotheliaTunnel2015 - ANR-15-CE18-0016 - AAPG2015 - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, and Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID
Subjects: RHOA, [SDV]Life Sciences [q-bio], Cell, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, medicine.disease_cause, Umbilical vein, 03 medical and health sciences, 0302 clinical medicine, medicine, Transcellular, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, biology, Chemistry, Fatty acid, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Docosahexaenoic acid, biology.protein, lipids (amino acids, peptides, and proteins), 030217 neurology & neurosurgery, Exotoxin, Homeostasis
Abstract: Metabolic studies and animal knockout models point to the critical role of polyunsaturated docosahexaenoic acid (22:6, DHA)-containing phospholipids (PLs) in physiology. Here, we study the impact of DHA-PLs on the dynamics of transendothelial cell macroapertures (TEMs) tunnels triggered by the RhoA GTPase inhibitory exotoxin C3 from Clostridium botulinum. Through lipidomic analyses, we show that primary human umbilical vein endothelial cells (HUVECs) subjected to DHA-diet undergo a 6-fold DHA-PLs enrichment in plasma membrane at the expense of monounsaturated OA-PLs. In contrast, OA-diet had almost no effect on PLs composition. Consequently, DHA treatment increases the nucleation rate of TEMs by 2-fold that we ascribe to a reduction of cell thickness. We reveal that the global transcellular area of cells remains conserved through a reduction of the width and lifetime of TEMs. Altogether, we reveal a homeostasis between plasma membrane DHA-PLs content and large-scale membrane dynamics.
Published: 2021

50. An ensemble model based on early predictors to forecast COVID-19 healthcare demand in France

Author: Paireau, Juliette, Andronico, Alessio, Hozé, Nathanaël, Layan, Maylis, Crepey, Pascal, Roumagnac, Alix, Lavielle, Marc, Boëlle, Pierre-Yves, Cauchemez, Simon, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Direction des maladies infectieuses - Infectious Diseases Division [Saint-Maurice], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Predict Services [Castelnau-le-Lez], Modélisation en pharmacologie de population (XPOP), Centre de Mathématiques Appliquées - Ecole Polytechnique (CMAP), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)
Subjects: Hospitalization, COVID-19, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Prediction, Model, Hospital admissions
Abstract: Short-term forecasting of the COVID-19 pandemic is required to facilitate the planning of COVID-19 healthcare demand in hospitals. Here, we evaluate the performance of 12 individual models and 19 predictors to anticipate French COVID-19 related healthcare needs from September 7th 2020 to March 6th 2021. We then build an ensemble model by combining the individual forecasts and test this model from March 7th to July 6th 2021. We find that inclusion of early predictors (epidemiological, mobility and meteorological predictors) can halve the root mean square error for 14-day ahead forecasts, with epidemiological and mobility predictors contributing the most to the improvement. On average, the ensemble model is the best or second best model, depending on the evaluation metric. Our approach facilitates the comparison and benchmarking of competing models through their integration in a coherent analytical framework, ensuring avenues for future improvements can be identified.
Published: 2021

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