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9,157 results on '"Emerging Infectious Diseases"'

201. Progress in Research on African Trypanosomes: Highlights from an Exceptional Decade

Author: Hutchinson, Sebastian, Calvo-Alvarez, Estefania, Tsagmo, Jean Marc, Lemos, Moara, Travaillé, Christelle, Rotureau, Brice, Bastin, Philippe, Biologie cellulaire des Trypanosomes - Trypanosome Cell Biology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), S.H. is supported by Roux and Marie Curie fellowships (funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 794979). Work in the laboratory is funded by the Institut Pasteur, INSERM, a French Government Investissement d’Avenir programme, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID) and the French National Agency for Scientific Research (project ANR-18-CE15-0012 TrypaDerm)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-18-CE15-0012,TrypaDerm,Comprendre la biologie des trypanosomes africains dans la peau(2018), and European Project: 794979,H2020-MSCA-IF-2017,scTRYPseq(2019)
Subjects: Microscopy, Flagellum, Genome, Tsetse fly, [SDV]Life Sciences [q-bio], parasitic diseases, Trypanosomes, Sleeping sickness, Trypanosoma brucei, Human African Trypanosomiasis, Reservoir, Skin
Abstract: International audience; In the late nineteenth century, Trypanosoma brucei was discovered as the parasitic protist responsible for Human African Trypanosomiasis (HAT), also known as sleeping sickness. It is transmitted by the bite of the tsetse fly where trypanosomes undergo several steps of differentiation, proliferation and migration that ultimately lead to the production of parasites than can again be infective for a mammalian host. Here, we review four major areas of trypanosome research that saw spectacular progress in knowledge over the last decade. The cell biology of the parasite can now be studied at unprecedented level thanks to the development of 3D electron microscopy, live imaging and super-resolution microscopy, revealing the architecture of all organelles, such as the flagellum that performs multiple essential functions. The omics area has lifted the basic vision of the genome sequence to a highly sophisticated appreciation of gene expression and chromatin organisation, with the ability to interrogate gene function thanks to advanced reverse genetics both at the individual and the global level. These developments were translated in vivo especially via imaging of the infection in the insect and the mammalian host. This resulted in a reconsideration of the life cycle, revealing the critical role of extravascular parasites in mammalian hosts where the skin now appears as a central reservoir for transmission. These findings will have an impact on monitoring and treating the disease in the field, as well as on the programme for elimination of HAT.
Published: 2022
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202. Genomic erosion and horizontal gene transfer shape functional differences of the ExlA toxin in Pseudomonas spp

Author: Viviana Job, Laura Gomez-Valero, Adèle Renier, Christophe Rusniok, Stephanie Bouillot, Viviane Chenal-Francisque, Erwan Gueguen, Annie Adrait, Mylène Robert-Genthon, Katy Jeannot, Peter Panchev, Sylvie Elsen, Marie-Odile Fauvarque, Yohann Couté, Carmen Buchrieser, Ina Attrée, Groupe Pathogenèse Bactérienne et Réponses Cellulaires / Bacterial Pathogenesis and Cellular Responses Group (IBS-PBRC), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, 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), Microbiologie, adaptation et pathogénie (MAP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Trafic et signalisation membranaires chez les bactéries (MTSB), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Etude de la dynamique des protéomes (EDyP), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), The work was supported by grants from Agence Nationale de la Recherche (ANR-15-CE11-0018-01), the Laboratory of Excellence GRAL, financed within the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS (ANR-17-EURE-0003) and the Fondation pour la Recherche Médicale (Team FRM 2017, DEQ20170336705) to I.A. We acknowledge the receipt of different Pseudomonas strains from the Collection of the Institut Pasteur (CIP). Work in the CB laboratory is financed by the Institut Pasteur and the grant n ANR-10-LABX-62-IBEID. Proteomic experiments were partially supported by ProFI (Proteomics French Infrastructure, ANR-10-INBS-08)., ANR-15-CE11-0018,HemoPseudo,Pneumonie hémorragique à Pseudomonas aeruginosa : étude de nouvelles stratégies de virulence(2015), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ATTREE, Ina, Pneumonie hémorragique à Pseudomonas aeruginosa : étude de nouvelles stratégies de virulence - - HemoPseudo2015 - ANR-15-CE11-0018 - AAPG2015 - VALID, CBH-EUR-GS - - CBH-EUR-GS2017 - ANR-17-EURE-0003 - EURE - VALID, and Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID
Subjects: Multidisciplinary, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; Two-partner secretion (TPS) is widespread in the bacterial world. The pore-forming TPS toxin ExlA of Pseudomonas aeruginosa is conserved in pathogenic and environmental Pseudomonas. While P. chlororaphis and P. entomophila displayed ExlA-dependent killing, P. putida did not cause damage to eukaryotic cells. ExlA proteins interacted with epithelial cell membranes; however, only ExlAPch induced the cleavage of the adhesive molecule E-cadherin. ExlA proteins participated in insecticidal activity toward the larvae of Galleria mellonella and the fly Drosophila melanogaster. Evolutionary analyses demonstrated that the differences in the C-terminal domains are partly due to horizontal movements of the operon within the genus Pseudomonas. Reconstruction of the evolutionary history revealed the complex horizontal acquisitions. Together, our results provide evidence that conserved TPS toxins in environmental Pseudomonas play a role in bacteria-insect interactions and discrete differences in CTDs may determine their specificity and mode of action toward eukaryotic cells.
Published: 2022
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203. C910 chemical compound inhibits the traffiking of several bacterial AB toxins with cross-protection against influenza virus

Author: Yu Wu, Nassim Mahtal, Eléa Paillares, Léa Swistak, Sara Sagadiev, Mridu Acharya, Caroline Demeret, Sylvie Van Der Werf, Florence Guivel-Benhassine, Olivier Schwartz, Serena Petracchini, Amel Mettouchi, Lucie Caramelle, Pierre Couvineau, Robert Thai, Peggy Barbe, Mathilde Keck, Priscille Brodin, Arnaud Machelart, Valentin Sencio, François Trottein, Martin Sachse, Gaëtan Chicanne, Bernard Payrastre, Florian Ville, Victor Kreis, Michel-Robert Popoff, Ludger Johannes, Jean-Christophe Cintrat, Julien Barbier, Daniel Gillet, Emmanuel Lemichez, TROTTEIN, François, Caractérisation d'un composé antitoxines bactériennes à large spectre - - ToxProtect_Larg_Spectr2019 - ANR-19-ASTR-0001 - ASTRID - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Research Laboratory on Drugs and Therapeutic Innovation - - LERMIT2010 - ANR-10-LABX-0033 - LABX - VALID, Toxines bactériennes - Bacterial Toxins, 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), Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), 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)-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), Service de Chimie Bio-Organique et de Marquage (SCBM), Seattle Children's Research Institute [Seattle, WA, USA], 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, Université Paris-Saclay, 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), CHU Lille, Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris] (IP), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie biologique des membranes et ciblage thérapeutique (CBMCT - UMR 3666 / U1143), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This work was funded by the joint ministerial program of Research and Development against Chemical, Biological, Radiological, Nuclear and Explosive risks ( CBRNE ), grants from the Agence Nationale de la Recherche ( ANR-19-ASTR-0001 ), Labex IBEID ( ANR-10-LABX-62-IBEID ), and the French Alternative Energies and Atomic Energy Commission ( CEA ). N.M., E.P., L.C., and F.V. were supported by DGA-MRIS/AID scholarships with CEA or Pasteur. SIMoS and SCBM are members of the Laboratory of Excellence LERMIT and were supported by a grant from the Agence Nationale de la Recherche ( ANR-10-LABX-33 )., ANR-19-ASTR-0001,ToxProtect_Larg_Spectr,Caractérisation d'un composé antitoxines bactériennes à large spectre(2019), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010), Virus et Immunité - Virus and immunity (CNRS-UMR3569), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV] Life Sciences [q-bio], Biological sciences, Multidisciplinary, [SDV]Life Sciences [q-bio], Microbiology
Abstract: International audience; The development of anti-infectives against a large range of AB-like toxin-producing bacteria includes the identification of compounds disrupting toxin transport through both the endolysosomal and retrograde pathways. Here, we performed a high-throughput screening of compounds blocking Rac1 proteasomal degradation triggered by the Cytotoxic Necrotizing Factor-1 (CNF1) toxin, which was followed by orthogonal screens against two toxins that hijack the endolysosomal (diphtheria toxin) or retrograde (Shiga-like toxin 1) pathways to intoxicate cells. This led to the identification of the molecule C910 that induces the enlargement of EEA1-positive early endosomes associated with sorting defects of CNF1 and Shiga toxins to their trafficking pathways. C910 protects cells against eight bacterial AB toxins and the CNF1-mediated pathogenic Escherichia coli invasion. Interestingly, C910 reduces influenza A H1N1 and SARS-CoV-2 viral infection in vitro. Moreover, parenteral administration of C910 to mice resulted in its accumulation in lung tissues and a reduction in lethal influenza infection.
Published: 2022
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204. Tocilizumab-treated convalescent COVID-19 patients retain the cross-neutralization potential against SARS-CoV-2 variants

Author: Chauvin, Camille, Levillayer, Laurine, Roumier, Mathilde, Nielly, Hubert, Roth, Claude, Karnam, Anupama, Bonam, Srinivasa Reddy, Bourgarit, Anne, Dubost, Clément, Bousquet, Aurore, Le Burel, Sébastien, Mestiri, Raphaële, Sene, Damien, Galland, Joris, Vasse, Marc, Groh, Matthieu, Le Marchand, Mathilde, Vassord-Dang, Camille, Gautier, Jean-François, Pham-Thi, Nhan, Verny, Christiane, Pitard, Bruno, Planchais, Cyril, Mouquet, Hugo, Paul, Richard, Simon-Loriere, Etienne, Bayry, Jagadeesh, Gilardin, Laurent, Sakuntabhai, Anavaj, Génétique fonctionnelle des maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Foch [Suresnes], Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, 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), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Nord, 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), CB - Centre Borelli - UMR 9010 (CB), Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Université Paris Cité (UPCité), Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Indian Institut of Technology [Palakkad] (ITT Palakkad), The University of Tokyo (UTokyo), This study is supported by the ANR funding (Flash COVID-19, ANR-20-COVI-0093-COVIMUNE). A.S. acknowledges the NIH grant no. U01AI151758. E.S.-L. acknowledges funding from the INCEPTION program (Investissements d’Avenir grant ANR-16-CONV-0005) and the French Government's Investissement d'Avenir programme, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant no. ANR-10-LABX-62-IBEID)., ANR-20-COVI-0093,COVIMUNE,Étude de la immunitaire interactive dans COVID-19(2020), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, treatment, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Immunology, Health sciences, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy
Abstract: International audience; Although tocilizumab treatment in severe and critical coronavirus disease 2019 (COVID-19) patients has proven its efficacy at the clinical level, there is little evidence supporting the effect of short-term use of interleukin-6 receptor blocking therapy on the B cell sub-populations and the cross-neutralization of SARS-CoV-2 variants in convalescent COVID-19 patients. We performed immunological profiling of 69 tocilizumab-treated and non-treated convalescent COVID-19 patients in total. We observed that SARS-CoV-2-specific IgG1 titers depended on disease severity but not on tocilizumab treatment. The plasma of both treated and non-treated patients infected with the ancestral variant exhibit strong neutralizing activity against the ancestral virus and the Alpha, Beta, and Delta variants of SARS-CoV-2, whereas the Gamma and Omicron viruses were less sensitive to seroneutralization. Overall, we observed that, despite the clinical benefits of short-term tocilizumab therapy in modifying the cytokine storm associated with COVID-19 infections, there were no modifications in the robustness of B cell and IgG responses to Spike antigens.
Published: 2023
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205. The New GPI-Anchored Protein, SwgA, Is Involved in Nitrogen Metabolism in the Pathogenic Filamentous Fungus Aspergillus fumigatus

Author: Marketa Samalova, Patricia Flamant, Rémi Beau, Mike Bromley, Maryse Moya-Nilges, Thierry Fontaine, Jean-Paul Latgé, Isabelle Mouyna, Aspergillus, Institut Pasteur [Paris] (IP), University of Manchester [Manchester], BioImagerie Photonique – Photonic BioImaging (UTechS PBI), This research was funded by l’Agence Nationale pour la Recherche (Afulnf ANR-16-CE92-0039), la Fondation pour la Recherche Médicale (DEQ20150331722), Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant ANR-10-LABX-62-IBEID), and an AIC grant. This work was also supported by the Wellcome trust grant 208396/Z/17/Z., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: Microbiology (medical), GPI-anchored protein, Aspergillus fumigatus, [SDV]Life Sciences [q-bio], cell wall, conidia, morphogenesis, Plant Science, nitrogen metabolism, Ecology, Evolution, Behavior and Systematics
Abstract: International audience; GPI-anchored proteins display very diverse biological (biochemical and immunological) functions. An in silico analysis has revealed that the genome of Aspergillus fumigatus contains 86 genes coding for putative GPI-anchored proteins (GPI-APs). Past research has demonstrated the involvement of GPI-APs in cell wall remodeling, virulence, and adhesion. We analyzed a new GPI-anchored protein called SwgA. We showed that this protein is mainly present in the Clavati of Aspergillus and is absent from yeasts and other molds. The protein, localized in the membrane of A. fumigatus, is involved in germination, growth, and morphogenesis, and is associated with nitrogen metabolism and thermosensitivity. swgA is controlled by the nitrogen regulator AreA. This current study indicates that GPI-APs have more general functions in fungal metabolism than cell wall biosynthesis.
Published: 2023
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206. Conidium Specific Polysaccharides in Aspergillus fumigatus

Author: Zhonghua Liu, Isabel Valsecchi, Rémy A. Le Meur, Catherine Simenel, J. Iñaki Guijarro, Catherine Comte, Laetitia Muszkieta, Isabelle Mouyna, Bernard Henrissat, Vishukumar Aimanianda, Jean-Paul Latgé, Thierry Fontaine, Aspergillus, Institut Pasteur [Paris] (IP), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Plateforme Technologique de RMN Biologique et HDX-MS - Biological NMR and HDX-MS Technological Platform, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Biologie des ARN des Pathogènes fongiques - RNA Biology of Fungal Pathogens, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mycologie moléculaire - Molecular Mycology, Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity (BPF), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This research was funded by the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (Grant No ANR-10-LABX-62-IBEID) and l’Agence Nationale pour la Recherche (AfuInf ANR-16-CE92-0039). The 800-MHz NMR spectrometer of the Institut Pasteur was partially funded by the Région Ile de France (SESAME 2014 NMRCHR grant no 4014526)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-16-CE92-0039,AfuInf,Protéome and polysaccharidome d'Aspergillus fumigatus lors des étapes précoces de l'infection(2016)
Subjects: Microbiology (medical), Aspergillus fumigatus, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], polysaccharidome, cell wall, conidium, Plant Science, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Ecology, Evolution, Behavior and Systematics
Abstract: International audience; Earlier studies have shown that the outer layers of the conidial and mycelial cell walls of Aspergillus fumigatus are different. In this work, we analyzed the polysaccharidome of the resting conidial cell wall and observed major differences within the mycelium cell wall. Mainly, the conidia cell wall was characterized by (i) a smaller amount of α-(1,3)-glucan and chitin; (ii) a larger amount of β-(1,3)-glucan, which was divided into alkali-insoluble and water-soluble fractions, and (iii) the existence of a specific mannan with side chains containing galactopyranose, glucose, and N-acetylglucosamine residues. An analysis of A. fumigatus cell wall gene mutants suggested that members of the fungal GH-72 transglycosylase family play a crucial role in the conidia cell wall β-(1,3)-glucan organization and that α-(1,6)-mannosyltransferases of GT-32 and GT-62 families are essential to the polymerization of the conidium-associated cell wall mannan. This specific mannan and the well-known galactomannan follow two independent biosynthetic pathways.
Published: 2023
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207. Systematic transcriptome analysis allows the identification of new type I and type II Toxin/Antitoxin systems located in the superintegron of Vibrio cholerae

Author: Evelyne Krin, Zeynep Baharoglu, Odile Sismeiro, Hugo Varet, Jean-Yves Coppée, Didier Mazel, Plasticité du Génome Bactérien - Bacterial Genome Plasticity (PGB), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Biomics (plateforme technologique), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), This study was supported by the Institut Pasteur, the Centre National de la Recherche Scientifique (CNRS-UMR3525), the French Government's Investissement d'Avenir program, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant n°ANR-10-LABX-62-IBEID) and the Fondation pour la Recherche Médicale grants DBF20160635736 and EQ U202103012569., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: [SDV]Life Sciences [q-bio], TA system Integron Antisense, General Medicine, Molecular Biology, Microbiology
Abstract: International audience; Vibrio cholerae N16961 genome encodes 18 type II Toxin/Antitoxin (TA) systems, all but one located inside gene cassettes of its chromosomal superintegron (SI). This study aims to investigate additional TA systems in this genome. We screened for all two-genes operons of uncharacterized function by analyzing previous RNAseq data. Assays on nine candidates, revealed one additional functional type II TA encoded by the VCA0497-0498 operon, carried inside a SI cassette. We showed that VCA0498 antitoxin alone and in complex with VCA0497 represses its own operon promoter. VCA0497-0498 is the second element of the recently identified dhiT/dhiA superfamily uncharacterized type II TA system. RNAseq analysis revealed that another SI cassette encodes a novel type I TA system: VCA0495 gene and its two associated antisense non-coding RNAs, ncRNA495 and ncRNA496. Silencing of both antisense ncRNAs lead to cell death, demonstrating the type I TA function. Both VCA0497 and VCA0495 toxins do not show any homology to functionally characterized toxins, however our preliminary data suggest that their activity may end up in mRNA degradation, directly or indirectly. Our findings increase the TA systems number carried in this SI to 19, preferentially located in its distal end, confirming their importance in this large cassette array.
Published: 2023
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208. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization

Author: Delphine Planas, Nell Saunders, Piet Maes, Florence Guivel-Benhassine, Cyril Planchais, Julian Buchrieser, William-Henry Bolland, Françoise Porrot, Isabelle Staropoli, Frederic Lemoine, Hélène Péré, David Veyer, Julien Puech, Julien Rodary, Guy Baele, Simon Dellicour, Joren Raymenants, Sarah Gorissen, Caspar Geenen, Bert Vanmechelen, Tony Wawina-Bokalanga, Joan Martí-Carreras, Lize Cuypers, Aymeric Sève, Laurent Hocqueloux, Thierry Prazuck, Félix A. Rey, Etienne Simon-Loriere, Timothée Bruel, Hugo Mouquet, Emmanuel André, Olivier Schwartz, 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), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, 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), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), 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)-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 libre de Bruxelles (ULB), University Hospitals Leuven [Leuven], Centre Hospitalier Régional d'Orléans (CHRO), Virologie Structurale - Structural Virology, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, The Opera system was co-funded by Institut Pasteur and the Région ile de France (DIM1Health). Work in the O.S. laboratory is funded by 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. Work in the 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. The H.M. laboratory is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), the INSERM, REACTing, EU (RECOVER) and Fondation de France (00106077) grants. The E.S.-L. laboratory is funded by Institut Pasteur, the INCEPTION program (Investissements d’Avenir grant ANR-16-CONV-0005) and the French Government’s Investissement d’Avenir programme, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID). G.B. acknowledges support from the Internal Funds KU Leuven under grant agreement C14/18/094, and the Research Foundation–Flanders (Fonds voor Wetenschappelijk Onderzoek–Vlaanderen, G0E1420N, G098321N). P.M. acknowledges support from a COVID-19 research grant of ‘Fonds Wetenschappelijk Onderzoek’/Research Foundation–Flanders (grant no. G0H4420N). S.D. is supported by the Fonds National de la Recherche Scientifique (FNRS, Belgium) and also acknowledges support from the Research Foundation–Flanders (Fonds voor Wetenschappelijk Onderzoek–Vlaanderen, G098321N) and from the European Union Horizon 2020 project MOOD (grant no. 874850)., 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-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-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 874850,H2020-SC1-2019-Single-Stage-RTD,MOOD(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]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-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)-École pratique des hautes études (EPHE), and European Project: 874850,MOOD
Subjects: MESH: Humans, MESH: Mutation, Multidisciplinary, MESH: ChAdOx1 nCoV-19, MESH: Neutralization Tests, MESH: Adult, MESH: Convalescence, MESH: Male, MESH: Antibodies, Monoclonal, MESH: Antibodies, Neutralizing, MESH: Belgium, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: COVID-19, MESH: Immunization, Secondary, MESH: SARS-CoV-2, MESH: Immune Evasion, MESH: BNT162 Vaccine, MESH: Phylogeny, MESH: Travel, MESH: Female, MESH: Antibodies, Viral
Abstract: The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1-3. It has since spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development4, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose. ispartof: NATURE vol:602 issue:7898 pages:671-+ ispartof: location:England status: published
Published: 2021
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209. Mechanisms supporting aminoadenine-based viral DNA genomes

Author: Pierre Alexandre Kaminski, Biologie des Bactéries pathogènes à Gram-positif - Biology of Gram-Positive Pathogens, 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), This study was funded from the French government’s Investissement d’Avenir program, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (Grant No. ANR-10-LABX-62-IBEID)., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: MESH: Adenine, Nucleotide phosphohydrolase, [SDV]Life Sciences [q-bio], MESH: Base Pairing, MESH: Adenine Nucleotides, Genome, Viral, DNA polymerase, Cellular and Molecular Neuroscience, Bacteriophages, MESH: Bacteriophages, MESH: Hydrogen Bonding, Adenylosuccinate synthase, Bacteriophage, Base Pairing, Molecular Biology, Pharmacology, Aminoadenine, Adenine Nucleotides, Adenine, Hydrogen Bonding, DNA, Cell Biology, MESH: DNA, Viral, DNA, Viral, Molecular Medicine, MESH: Genome, Viral
Abstract: International audience; Bacteriophage genomes are the richest source of modified nucleobases of any life form. Of these, 2,6 diaminopurine, which pairs with thymine by forming three hydrogen bonds violates Watson and Crick’s base pairing. 2,6 diaminopurine initially found in the cyanophage S-2L is more widespread than expected and has also been detected in phage infecting Gram-negative and Gram-positive bacteria. The biosynthetic pathway for aminoadenine containing DNA as well as the exclusion of adenine are now elucidated. This example of a natural deviation from the genetic code represents only one of the possibilities explored by nature and provides a proof of concept for the synthetic biology of non-canonical nucleic acids.
Published: 2021
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210. Model-based assessment of Chikungunya and O’nyong-nyong virus circulation in Mali in a serological cross-reactivity context

Author: Hozé, Nathanaël, Diarra, Issa, Sangaré, Abdoul Karim, Pastorino, Boris, Pezzi, Laura, Kouriba, Bourèma, Sagara, Issaka, Dabo, Abdoulaye, Djimdé, Abdoulaye, Thera, Mahamadou Ali, Doumbo, Ogobara K., de Lamballerie, Xavier, Cauchemez, Simon, 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), 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), Malaria Research and Training Center [Bamako, Mali], Université de Bamako, Centre d'Infectiologie Charles Mérieux, Bamako, Mali, Laboratoire de Virologie [UNIV Corse-Inserm] (EA7310), Université Pascal Paoli (UPP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nathanaël Hozé and Simon Cauchemez acknowledge financial support from the AXA Research Fund, the Investissement d’Avenir program, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program (Grant ANR-10-LABX-62-IBEID), the INCEPTION project (PIA/ANR-16-CONV-0005), We thank the European Union’s Horizon 2020 research and innovation program under ZIKAlliance grant agreement No. 734548 and the Minister of Health and Hygiene of Mali supported this work through the subvention no. 2016/668116-0 from the Mali World Health Organization Local Office., We dedicate this article to Ogobara K. Doumbo, who initiated this project before he passed. May he rest in peace. We thank Christine Isnard from EFS, Marseille for invaluable technical contribution. We are grateful to Ismaila Thera, from MRTC, Bamako who developed the electronic database using ODK and provided the data management service for the study. We also thank the study district health officers and the study population for their cooperation. Specifically, we are indebted to Hamma Maiga, Bakary Sidibé, Modibo Diarra, Kassoum Kayentao, Souleymane Dama, Hamidou Niangaly, Amadou Bamadio, Hamadoun Diaité, Karim Traoré and Balla Diarra for their support to field investigations., 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: 734548,ZIKAlliance(2016), Limouzin, Cécile, 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, A global alliance for Zika virus control and prevention - ZIKAlliance - 2016-10-01 - 2019-09-30 - 734548 - VALID, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pascal Paoli (UPP)
Subjects: Statistical methods, Viral epidemiology, Epidemiology, viruses, Science, MESH: Algorithms, [MATH] Mathematics [math], MESH: Chikungunya Fever, Cross Reactions, Mali, Sensitivity and Specificity, Article, MESH: Cross Reactions, Seroepidemiologic Studies, MESH: Martinique, parasitic diseases, Humans, O'nyong-nyong Virus, Martinique, [MATH]Mathematics [math], Models, Statistical, MESH: Seroepidemiologic Studies, MESH: Humans, Reproducibility of Results, virus diseases, MESH: Chikungunya virus, MESH: Mali, MESH: Sensitivity and Specificity, MESH: O'nyong-nyong Virus, MESH: Reproducibility of Results, Viral infection, Chikungunya Fever, Chikungunya virus, Algorithms, MESH: Models, Statistical
Abstract: Serological surveys are essential to quantify immunity in a population but serological cross-reactivity often impairs estimates of the seroprevalence. Here, we show that modeling helps addressing this key challenge by considering the important cross-reactivity between Chikungunya (CHIKV) and O’nyong-nyong virus (ONNV) as a case study. We develop a statistical model to assess the epidemiology of these viruses in Mali. We additionally calibrate the model with paired virus neutralization titers in the French West Indies, a region with known CHIKV circulation but no ONNV. In Mali, the model estimate of ONNV and CHIKV prevalence is 30% and 13%, respectively, versus 27% and 2% in non-adjusted estimates. While a CHIKV infection induces an ONNV response in 80% of cases, an ONNV infection leads to a cross-reactive CHIKV response in only 22% of cases. Our study shows the importance of conducting serological assays on multiple cross-reactive pathogens to estimate levels of virus circulation., O’nyong nyong and Chikungunya virus are arboviruses present in Africa but their prevalence is unknown, partly due to high antibody cross-reactivity with one another. Here, the authors develop a statistical model that accounts for cross-reactivity to characterise circulation of both viruses from seroprevalence surveys.
Published: 2021
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211. Impact of booster vaccination on the control of COVID-19 in the context of waning immunity: Application to France in the autumn-winter 2021-2022

Author: Bosetti, Paolo, Tran Kiem, Cécile, Andronico, Alessio, Paireau, Juliette, Levy-Bruhl, Daniel, ALTER, Lise, Fontanet, Arnaud, Cauchemez, Simon, 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), 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, 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), 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,VEO, Noel, Anne-Laure, 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, Versatile Emerging infectious disease Observatory - VEO - - H2020-SC1-2019-Single-Stage-RTD2020-01-01 - 2024-12-31 - 874735 - VALID, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège Doctoral, 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), and European Project: 874735,H2020-SC1-2019-Single-Stage-RTD,VEO(2020)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: Europe is confronted with a large COVID-19 wave caused by the Delta variant in autumnwinter 2021-2022. Using a mathematical model applied to Metropolitan France, we find that the hospitalisation peak might be reduced by 25%, 36% and 43% if boosters are administered to those aged 65+, 50+ or 18+, respectively, with a delay of 5 months between the second and third dose. Ten percent reduction in transmission rates might further reduce peak size by 41%, indicating that even small increases in protective behaviours may play a critical role to mitigate the wave.Most European countries have experienced an important rise in SARS-CoV-2 infections and hospitalisations in the Autumn 2021. In response to this resurgence and to the reported partial decay of immunity, countries have started administering vaccine booster doses, relying on different eligibility criteria. Here, we present modelling analyses assessing different administration strategies for booster doses that informed the recommendations of the French National Immunization Technical Advisory Group (Haute Autorité de Santé) in the context of Metropolitan France.
Published: 2021

212. Autoantibodies against type I IFNs in patients with Ph-negative myeloproliferative neoplasms

Author: Oscar Borsani, Paul Bastard, Jérémie Rosain, Adrian Gervais, Emanuela Sant’Antonio, Daniele Vanni, Ilaria Carola Casetti, Daniela Pietra, Chiara Trotti, Silvia Catricalà, Virginia Valeria Ferretti, Luca Malcovati, Luca Arcaini, Jean-Laurent Casanova, Alessandro Borghesi, Elisa Rumi, University of Pavia, Human genetics of infectious diseases : Mendelian predisposition (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 (UPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Azienda Usl Toscana centro [Firenze], Fondazione IRCCS Policlinico San Matteo [Pavia], Università di Pavia, Howard Hughes Medical Institute (HHMI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Studies performed at the Department of Hematology, Fondazione IRCCS Policlinico San Matteo and Department of Molecular Medicine, University of Pavia were supported by grants from the Italian Ministry of Health for young researchers (GR-2016-02361272) (E.R.) and by Associazione Italiana per la Ricerca sul Cancro (AIRC: IG 2021 ID 25703) through the project 'Actionable targets in clonal progression and systemic spreading of myeloid neoplasms,' (IG 2021 ID 25703) (E.R.) MYNERVA project (Project Code: 21267) (E.R. and L.M.). This work was supported by The European Union’s Horizon 2020 research and innovation program (ATAC, 101003650), the Center for Innovative Medicine at Karolinska Institutet, the Swedish Research Council, the Knut and Alice Wallenberg Foundation (KAW). The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institute of Allergy and Infectious Diseases (NIAID) (grants R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health Clinical and Translational Science Award (CTSA) program (UL1TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), ANR grants (ANR-14-CE14-0008-01, ANR-18-CE15-0020-02, ANR-20-CE93-003, ANR-20-CO11-000,1 and ANR-21-COVR-0039), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANR-20-COVI-0003), ANRS Nord-Sud (ANRS-COV05), the European Union’s Horizon 2020 Research and Innovation Program (grant agreement no. 824110) (EASI-Genomics), the Square Foundation, Grandir-Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Fondation du Souffle, Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University of Paris. P.B. received support from the French Foundation for Medical Research (FRM, EA20170638020) and was supported by the PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller)., ANR-14-CE14-0008,IEIHSEER,L'encéphalite Herpétique de l'enfant résulte de déficits héréditaires d'immunité contre l'HSV-1: une exception ou une règle?(2014), ANR-18-CE15-0020,SEAe-HostFactors,Facteurs de susceptibilité de l'hôte à l'encéphalite pédiatrique en Asie du Sud Est(2018), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), Università degli Studi di Pavia = University of Pavia (UNIPV), 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), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: MESH: Interferon Type I, MESH: Humans, Myeloproliferative Disorders, [SDV]Life Sciences [q-bio], Immunology, Cell Biology, Hematology, Biochemistry, Neoplasms, Interferon Type I, MESH: Autoantibodies, Humans, MESH: Neoplasms, ComputingMilieux_MISCELLANEOUS, risk, MESH: Myeloproliferative Disorders, Autoantibodies
Abstract: International audience
Published: 2021
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213. A novel SARS-CoV-2 related coronavirus in bats from Cambodia

Author: Deborah, Delaune, Vibol, Hul, Erik A, Karlsson, Alexandre, Hassanin, Tey Putita, Ou, Artem, Baidaliuk, Fabiana, Gámbaro, Matthieu, Prot, Vuong Tan, Tu, Sokha, Chea, Lucy, Keatts, Jonna, Mazet, Christine K, Johnson, Philippe, Buchy, Philippe, Dussart, Tracey, Goldstein, Etienne, Simon-Lorière, Veasna, Duong, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Université Paris-Saclay, Unité de Virologie / Virology Unit [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), 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), 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), Université Paris Cité (UPCité), Wildlife Conservation Society [Phnom Penh, Cambodia], Wildlife Conservation Society (WCS), University of California [Davis] (UC Davis), University of California (UC), This study was made possible by the generous support of the American people through the United States Agency for International Development (USAID) Emerging Pandemic Threats PREDICT project (cooperative agreement number GHN-A-OO-09-00010-00 and AID-OAA-A-14-00102), with a specific extension for the testing reported here. V.H. is supported by a scholarship from the French Government (BGF) for his Ph.D. E.S.L. acknowledges funding from the French Government’s Investissement d’Avenir program, ‘INCEPTION’ (ANR-16-CONV-0005), and Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (ANR-10-LABX-62-IBEID). In 2010, the fieldwork was supported by the National Authority for Preah Vihear, UNESCO, 'Société des amis du Muséum et du Jardin des Plantes', and the Muséum national d’Histoire naturelle., 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-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut de Recherche Biomédicale des Armées (IRBA), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Dussart, Philippe, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, and Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID
Subjects: Epidemiology, viruses, MESH: Spike Glycoprotein, Coronavirus, MESH: Amino Acid Sequence, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Chiroptera, MESH: COVID-19, MESH: Animals, Viral, skin and connective tissue diseases, MESH: Phylogeny, Lung, Phylogeny, MESH: Evolution, Molecular, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genome, virus diseases, MESH: Chiroptera, Spike Glycoprotein, Infectious Diseases, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Pneumonia & Influenza, MESH: Genome, Viral, Cambodia, Evolution, Science, MESH: Sequence Alignment, Genome, Viral, Article, Evolution, Molecular, Vaccine Related, Biodefense, [SDV.BID.SPT] Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Animals, MESH: SARS-CoV-2, Amino Acid Sequence, SARS-CoV-2, Prevention, MESH: Cambodia, fungi, Molecular, COVID-19, Pneumonia, Coronavirus, body regions, Emerging Infectious Diseases, Good Health and Well Being, Molecular evolution, Metagenomics, Sequence Alignment
Abstract: Knowledge of the origin and reservoir of the coronavirus responsible for the ongoing COVID-19 pandemic is still fragmentary. To date, the closest relatives to SARS-CoV-2 have been detected in Rhinolophus bats sampled in the Yunnan province, China. Here we describe the identification of SARS-CoV-2 related coronaviruses in two Rhinolophus shameli bats sampled in Cambodia in 2010. Metagenomic sequencing identifies nearly identical viruses sharing 92.6% nucleotide identity with SARS-CoV-2. Most genomic regions are closely related to SARS-CoV-2, with the exception of a region of the spike, which is not compatible with human ACE2-mediated entry. The discovery of these viruses in a bat species not found in China indicates that SARS-CoV-2 related viruses have a much wider geographic distribution than previously reported, and suggests that Southeast Asia represents a key area to consider for future surveillance for coronaviruses., In this study, Delaune et al., isolate and characterise a SARS-CoV-2-related coronavirus from two bats sampled in Cambodia. Their findings suggest that the geographic distribution of SARS-CoV-2-related viruses is wider than previously reported.
Published: 2021
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214. Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans

Author: O’neill, Mary, Quach, Hélène, Pothlichet, Julien, Aquino, Yann, Bisiaux, Aurélie, Zidane, Nora, Deschamps, Matthieu, Libri, Valentina, Hasan, Milena, Zhang, Shen-Ying, Zhang, Qian, Matuozzo, Daniela, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, Naffakh, Nadia, Rotival, Maxime, Quintana-Murci, Lluis, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Éco-Anthropologie (EAE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Diaccurate SAS, Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), 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), Rockefeller University [New York], Howard Hughes Medical Institute (HHMI), Biologie des ARN et virus influenza - RNA Biology of Influenza Virus, Collège de France (CdF (institution)), This work was supported by the Institut Pasteur, the Collège de France, the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10- LABX-62-IBEID) and 'Milieu Intérieur' (ANR-10-LABX-69-01), the Fondation de France (n°00106080), and the Fondation pour la Recherche Médicale (Equipe FRM DEQ20180339214). MO’N was supported by a European Molecular Biology Organization long-term fellowship (ALTF 229-2017)., 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), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Éco-Anthropologie (EA), Collège Doctoral, Institut Pasteur [Paris] (IP)-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)-Université Paris Cité (UPCité), Biologie des ARN et virus influenza - RNA Biology of Influenza Virus (CNRS-UMR3569), Collège de France - Chaire Génomique humaine et évolution, European Project: ALTF 229-2017, Gestionnaire, Hal Sorbonne Université, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - 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, and European Molecular Biology Organization long-term fellowship - ALTF 229-2017 - INCOMING
Subjects: Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, population, Black People, GPI-Linked Proteins, Monocytes, influenza virus, White People, transcriptomics, Young Adult, Hypothesis and Theory, Influenza, Human, Immunology and Allergy, Humans, Sequence Analysis, RNA, ancestry, Receptors, IgG, Middle Aged, single-cell ‘omics, Influenza A virus, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, single-cell 'omics, Single-Cell Analysis, Ribosomes
Abstract: International audience; There is considerable inter-individual and inter-population variability in response to viruses. The potential of monocytes to elicit type-I interferon responses has attracted attention to their role in viral infections. Here, we use single-cell RNA-sequencing to characterize the role of cellular heterogeneity in human variation of monocyte responses to influenza A virus (IAV) exposure. We show widespread inter-individual variability in the percentage of IAV-infected monocytes. Notably, individuals with high cellular susceptibility to IAV are characterized by a lower activation at basal state of an IRF/STAT-induced transcriptional network, which includes antiviral genes such as IFITM3 , MX1 and OAS3 . Upon IAV challenge, we find that cells escaping viral infection display increased mRNA expression of type-I interferon stimulated genes and decreased expression of ribosomal genes, relative to both infected cells and those never exposed to IAV. We also uncover a stronger resistance of CD16 + monocytes to IAV infection, together with CD16 + -specific mRNA expression of IL6 and TNF in response to IAV. Finally, using flow cytometry and bulk RNA-sequencing across 200 individuals of African and European ancestry, we observe a higher number of CD16 + monocytes and lower susceptibility to IAV infection among monocytes from individuals of African-descent. Based on these data, we hypothesize that higher basal monocyte activation, driven by environmental factors and/or weak-effect genetic variants, underlies the lower cellular susceptibility to IAV infection of individuals of African ancestry relative to those of European ancestry. Further studies are now required to investigate how such cellular differences in IAV susceptibility translate into population differences in clinical outcomes and susceptibility to severe influenza.
Published: 2021
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215. Monoclonal antibody-mediated neutralization of SARS-CoV-2 in an IRF9-deficient child

Author: Marianne Burgard, George C. Hartoularos, Martin Castelle, Alice Hadchouel, Laureline Berteloot, Romain Lévy, Bénédicte Neven, Jean-Laurent Casanova, Qian Zhang, Karim Dorgham, Lucy Bizien, Chun Jimmie Ye, Hanène Abid, Tom Toin, Isabelle Melki, Peng Zhang, Nadhira Houhou-Fidouh, Paul Bastard, Emmanuelle Jouanguy, Charlotte Roy, Flore Rozenberg, Guy Gorochov, Service d'immuno-hématologie pédiatrique [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), Rockefeller University [New York], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), Hôpital Robert Debré Paris, Hôpital Robert Debré, Service de Pneumologie Allergologie [CHU Necker], University of California (UC), CHU Necker - Enfants Malades [AP-HP], MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [CHU Necker], Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de Génétique Médicale [CHU Necker], Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [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-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), Gestionnaire, HAL Sorbonne Université 5, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères - - GENVIR2020 - ANR-20-CE93-0003 - AAPG2020 - VALID, Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19. - - AABIFNCOV2020 - ANR-20-CO11-0001 - COVID-19 - VALID, Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant. - - GenMIS-C2021 - ANR-21-COVR-0039 - COVID-19 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of California, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: medicine.drug_class, Viremia, Monoclonal antibody, Antibodies, Monoclonal, Humanized, Virus, Neutralization, 03 medical and health sciences, Immunocompromised Host, 0302 clinical medicine, Interferon, medicine, Genetics, Humans, 030304 developmental biology, Blood type, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Multidisciplinary, business.industry, SARS-CoV-2, COVID-19, interferon, Viral Load, Biological Sciences, medicine.disease, Antibodies, Neutralizing, Interferon-Stimulated Gene Factor 3, gamma Subunit, 3. Good health, Upper respiratory tract infection, Child, Preschool, inherited primary immunodeficiency, Immunology, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, RNA-seq, business, Viral load, 030215 immunology, medicine.drug
Abstract: Significance Life-threatening COVID-19 pneumonia can be caused by rare inborn errors of type I interferon (IFN) immunity, or by autoantibodies neutralizing IFN-α2 or IFN-ω. In 2018, we reported a girl with critical influenza pneumonia due to inherited IRF9 deficiency, a component of the ISGF-3 transcription factor. We report the course of COVID-19 in the same patient. She was admitted on day 1 of upper respiratory tract infection with viremia. Administration of SARS-CoV-2–specific neutralizing monoclonal antibodies on day 2 prevented the development of pneumonia. SARS-CoV-2–specific monoclonal antibodies were sufficient to overcome a lack of ISGF-3– and IRF9-dependent type I and type III IFN immunity to the virus. They should be considered in selected children at high risk of life-threatening COVID-19., We describe an unvaccinated child at risk for life-threatening COVID-19 due to an inherited deficiency of IRF9, which governs ISGF-3–dependent responses to type I and III interferons (IFN). She was admitted, with a high nasal SARS-CoV-2 load on day 1 of upper respiratory tract infection. She was viremic on day 2 and received casirivimab and imdevimab. Her clinical manifestations and viremia disappeared on days 3 and 4, respectively. Circulating SARS-CoV-2 virus induced the expression of IFN-stimulated genes in leukocytes on day 1, whereas the secretion of blood type I IFNs, which peaked on day 4, did not. Antibody-mediated SARS-CoV-2 neutralization is, therefore, sufficient to overcome a deficiency of antiviral IFNs.
Published: 2021
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216. The genomic signatures of natural selection in admixed human populations

Author: Lluis Quintana-Murci, S. Cuadros-Espinoza, Guillaume Laval, Etienne Patin, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège de France - Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral, Sorbonne Université (SU), S.C.-E. is supported by Sorbonne Université Doctoral College, the Inception program (Investissement d’Avenir grant ANR-16-CONV-0005), and the Institut Pasteur. The laboratory of human evolutionary genetics is supported by the Institut Pasteur, the Collège de France, the CNRS, the Fondation Allianz-Institut de France, the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID) and 'Milieu Intérieur' (ANR-10-LABX-69-01), the Fondation de France (No. 00106080), the Fondation pour la Recherche Médicale (équipe FRM DEQ20180339214), and the French National Research Agency (ANR-19-CE35-0005)., 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-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), and ANR-19-CE35-0005,MORTUI,Impact des Pandémies Passées sur l'Evolution de l'Homme : Une Etude Archéo-Génomique des Victimes de la Peste Noire(2019)
Subjects: Gene Flow, Population, Introgression, Black People, genome scan, Biology, Polymorphism, Single Nucleotide, Article, Gene flow, 03 medical and health sciences, 0302 clinical medicine, genetic adaptation, positive selection, Genetics, Humans, Selection, Genetic, education, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Genetic diversity, education.field_of_study, Natural selection, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Genomics, Background selection, Apolipoprotein L1, Adaptation, Physiological, 3. Good health, Lactase persistence, Genetics, Population, human population genetics, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Evolutionary biology, admixture, 030217 neurology & neurosurgery, Neutral mutation
Abstract: Admixture has been a pervasive phenomenon in human history, shaping extensively the patterns of population genetic diversity. There is increasing evidence to suggest that admixture can also facilitate genetic adaptation to local environments, i.e., admixed populations acquire beneficial mutations from source populations, a process that we refer to as adaptive admixture. However, the role of adaptive admixture in human evolution and the power to detect it are poorly characterized. Here, we use extensive computer simulations to evaluate the power of several neutrality statistics to detect natural selection in the admixed population, accounting for background selection and assuming different admixture scenarios. We show that two statistics based on admixture proportions, Fadm and LAD, show high power to detect mutations that are beneficial in the admixed population, whereas iHS and FST falsely detect neutral mutations that have been selected in the source populations only. By combining Fadm and LAD into a single statistic, we scanned the genomes of 15 worldwide, admixed populations for signatures of adaptive admixture. We confirm that lactase persistence and resistance to malaria have been under adaptive admixture in West Africa and in Madagascar, North Africa and South Asia, respectively. Our approach also uncovers new cases of adaptive admixture, including the APOL1/MYH9 locus in the Fulani nomads and PKN2 in East Indonesians, involved in resistance to infection and metabolism, respectively. Collectively, our study provides new evidence that adaptive admixture has occurred in multiple human populations, whose genetic history is characterized by periods of isolation and spatial expansions resulting in increased gene flow.Author summaryAdaptive introgression, i.e., the acquisition of adaptive traits through hybridization with another species, is a well-documented phenomenon in evolution. Conversely, adaptive admixture, i.e., the acquisition of adaptive traits through admixture between populations of the same species, is poorly described. In this study, we evaluate the importance of adaptive admixture in human recent evolutionary history. We first determine the expected signatures of adaptive admixture on patterns of genomic diversity, using realistic simulations. We then identify the methods that are the most powerful to detect such molecular signatures. Finally, by using the methods identified as the most powerful, we search for cases of adaptive admixture in the genomes of 15 admixed populations from around the globe. We find evidence that adaptive admixture has occurred in several populations from Northeast Africa, Southeast Asia and Oceania. This study suggests that admixture has indeed facilitated human genetic adaptation, particularly at genes involved in metabolism and resistance against pathogens.
Published: 2021
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217. Listeriolysin S: A bacteriocin from Listeria monocytogenes that induces membrane permeabilization in a contact-dependent manner

Author: Meza-Torres, Jazmín, Lelek, Mickaël, Quereda, Juan, Sachse, Martin, Manina, Giulia, Ershov, Dmitry, Tinevez, Jean-Yves, Radoshevich, Lilliana, Maudet, Claire, Chaze, Thibault, Giai Gianetto, Quentin, Matondo, Mariette, Lecuit, Marc, Martin-Verstraete, Isabelle, Zimmer, Christophe, Bierne, Hélène, Dussurget, Olivier, Cossart, Pascale, Pizarro-Cerdá, Javier, Yersinia, Institut Pasteur [Paris] (IP), Interactions Bactéries-Cellules, Université Paris Cité (UPCité), Université Sorbonne Paris Cité (USPC), Imagerie et Modélisation - Imaging and Modeling, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universidad Cardenal Herrera-CEU (CEU-UCH), Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Individualité microbienne et infection - Microbial Individuality and Infection, Hub d'analyse d'images - Image Analysis Hub (Platform) (IAH), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, University of Iowa [Iowa City], Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay, 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), This work received financial support from Institut Pasteur, Institut Carnot Pasteur Microbes et Santé (PasteurInnov Grant LLS-Bact), Région Ile-de-France (DIM-MALINF), and Fondation pour la Recherche Médicale (Grant FDT201904008152) (to J.M.-T.). J.J.Q. is supported by a 'Ramón y Cajal' contract from the Spanish Ministry of Science, Innovation and Universities (RYC-2018-024985-I). The Yersinia Research Unit is a member of the LabEX Integrative Biology of Emerging Infectious Diseases (ANR LBX-62 IBEID), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Bierne, Hélène, and Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID
Subjects: MESH: Cytoplasm, [SDV]Life Sciences [q-bio], microfluidic microscopy, MESH: Listeria monocytogenes, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, contact-dependent inhibition (CDI), [SDV] Life Sciences [q-bio], MESH: Bacteriocins, bacteriocin, MESH: Hemolysin Proteins, Listeria monocytogenes (Lm), MESH: Adenosine Triphosphate, Listeriolysin S (LLS), [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Cell Membrane
Abstract: International audience; Significance Listeria monocytogenes ( Lm ) is a bacterial pathogen that causes listeriosis, a foodborne disease characterized by gastroenteritis, meningitis, bacteremia, and abortions in pregnant women. The most severe human listeriosis outbreaks are associated with a subset of Lm hypervirulent clones that encode the bacteriocin Listeriolysin S (LLS), which modifies the gut microbiota and allows efficient Lm gut colonization and invasion of deeper organs. Our present work identifies the killing mechanism displayed by LLS to outcompete gut commensal bacteria, demonstrating that it induces membrane permeabilization and membrane depolarization of target bacteria. Moreover, we show that LLS is a thiazole/oxazole–modified microcin that displays a contact-dependent inhibition mechanism.
Published: 2021
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218. SARS-CoV-2 transmission across age groups in France and implications for control

Author: Tran Kiem, Cécile, Bosetti, Paolo, Paireau, Juliette, Crepey, Pascal, Salje, Henrik, Lefrancq, Noémie, Fontanet, Arnaud, Benamouzig, Daniel, Boëlle, Pierre-Yves, Desenclos, Jean-Claude, Opatowski, Lulla, Cauchemez, Simon, 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], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), University of Cambridge [UK] (CAM), 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), Conservatoire National des Arts et Métiers [CNAM] (CNAM), 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), Centre de sociologie des organisations (Sciences Po, CNRS) (CSO), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), 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, 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), Santé Publique France, the 101003589 project (PIA/ANR-16-CONV-0005), the European Union’s Horizon 2020 research and innovation program under grant 101003589 (RECOVER), AXA and Institut 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-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Université Paris Cité (UPCité), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), 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., Tran Kiem, Cécile [0000-0003-0563-8428], Paireau, Juliette [0000-0002-5143-6256], Crépey, Pascal [0000-0003-1852-0752], Salje, Henrik [0000-0003-3626-4254], Lefrancq, Noemie [0000-0001-5991-6169], Desenclos, Jean-Claude [0000-0003-0892-8252], Cauchemez, Simon [0000-0001-9186-4549], Apollo - University of Cambridge Repository, Lassailly-Bondaz, Anne, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, 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 Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], 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 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), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], 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], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Hôpital Paul Brousse, Jonchère, Laurent, and Lefrancq, Noémie [0000-0001-5991-6169]
Subjects: Adult, Male, 141, COVID-19 Vaccines, Adolescent, Statistical methods, Epidemiology, Science, [SDV]Life Sciences [q-bio], Physical Distancing, Young Adult, 631/114/2397, Humans, Computational models, Transmission, Computer Simulation, 692/308/174, 129, Child, Pandemics, 631/326/596/4130, Aged, Aged, 80 and over, SARS-CoV-2, Age Factors, Infant, Newborn, article, COVID-19, Infant, Middle Aged, 631/114/2415, Hospitalization, [SDV] Life Sciences [q-bio], [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Child, Preschool, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, SARS - CoV-2
Abstract: The shielding of older individuals has been proposed to limit COVID-19 hospitalizations while relaxing general social distancing in the absence of vaccines. Evaluating such approaches requires a deep understanding of transmission dynamics across ages. Here, we use detailed age-specific case and hospitalization data to model the rebound in the French epidemic in summer 2020, characterize age-specific transmission dynamics and critically evaluate different age-targeted intervention measures in the absence of vaccines. We find that while the rebound started in young adults, it reached individuals aged ≥80 y.o. after 4 weeks, despite substantial contact reductions, indicating substantial transmission flows across ages. We derive the contribution of each age group to transmission. While shielding older individuals reduces mortality, it is insufficient to allow major relaxations of social distancing. When the epidemic remains manageable (R close to 1), targeting those most contributing to transmission is better than shielding at-risk individuals. Pandemic control requires an effort from all age groups., In this study, Tran Kiem et al. examine the contribution of different age groups to COVID-19 transmission. Using data from the French epidemic in summer 2020, they report that while individuals aged 80 years and older are more at risk, pandemic control in the absence of vaccines required measures targeted at all age groups.
Published: 2021
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219. Streptococcus pneumoniae Infection Promotes Histone H3 Dephosphorylation by Modulating Host PP1 Phosphatase

Author: Michael G. Connor, Matthew J. G. Eldridge, Christine Chevalier, Melanie Hamon, Orhan Rasid, Wenyang Dong, Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris] (IP), Université Sorbonne Paris Cité (USPC), Work in the M.A.H. laboratory received financial support from Institut Pasteur and the National Research Agency (ANR-EPIBACTIN). W.D. is part of the Pasteur-Paris University (PPU) International PhD Program, a project which has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 665807. W.D. is 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. M.C. is supported by the Pasteur Foundation Fellowship. M.J.G.E. is supported by a fellowship from the French Government’s Investissement d’Avenir program, the Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID)., ANR-17-CE12-0007,EpiBactIn,Modifications epigenomiques induites par l'interaction hote-bacteries(2017), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), and Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Transcription, Genetic, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine.disease_cause, Histones, Serine, Phosphoserine, 0302 clinical medicine, Phosphoprotein Phosphatases, histone modification, Phosphorylation, lcsh:QH301-705.5, Epigenomics, 0303 health sciences, biology, Chemistry, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], pneumolysin, Cell biology, 3. Good health, Histone, Streptococcus pneumoniae, Host-Pathogen Interactions, Streptolysins, Female, Intracellular, Phosphatase, Pneumococcal Infections, General Biochemistry, Genetics and Molecular Biology, Cell Line, Microbiology, Dephosphorylation, 03 medical and health sciences, Histone H3, Bacterial Proteins, protein phosphatase 1, medicine, Animals, Humans, 030304 developmental biology, Inflammation, Pneumolysin, 030306 microbiology, bacterial infection, Protein phosphatase 1, SpxB, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Gene Expression Regulation, Bacterial, Hydrogen Peroxide, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Mice, Inbred C57BL, 030104 developmental biology, H3S10 dephosphorylation, lcsh:Biology (General), biology.protein, 030217 neurology & neurosurgery
Abstract: Summary: Pathogenic bacteria can alter host gene expression through post-translational modifications of histones. We show that a natural colonizer, Streptococcus pneumoniae, induces specific histone modifications, including robust dephosphorylation of histone H3 on serine 10 (H3S10), during infection of respiratory epithelial cells. The bacterial pore-forming toxin pneumolysin (PLY), along with the pyruvate oxidase SpxB responsible for H2O2 production, play important roles in the induction of this modification. The combined effects of PLY and H2O2 trigger host signaling that culminates in H3S10 dephosphorylation, which is mediated by the host cell phosphatase PP1. Strikingly, S. pneumoniae infection induces dephosphorylation and subsequent activation of PP1 catalytic activity. Colonization of PP1 catalytically deficient cells results in impaired intracellular S. pneumoniae survival and infection. Interestingly, PP1 activation and H3S10 dephosphorylation are not restricted to S. pneumoniae and appear to be general epigenomic mechanisms favoring intracellular survival of pathogenic bacteria. : Dong et al. show that Streptococcus pneumoniae infection induces histone H3 dephosphorylation in lung epithelial cells, through two bacterial factors, PLY and SpxB. Infection-triggered activation of the host phosphatase PP1 is required for this histone modification and efficient intracellular infection. Keywords: histone modification, Streptococcus pneumoniae, H3S10 dephosphorylation, protein phosphatase 1, bacterial infection, pneumolysin, SpxB
Published: 2020
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220. Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins

Author: Melanie Hamon, Francis Impens, Matthew J. G. Eldridge, Jorge M. Pereira, Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris], Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), MJGE is supported by a fellowship from the French Government’s Investissement d’Avenir program, the Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID). Work in the M.A.H. laboratory received financial support from the Institut Pasteur and the National Research Agency (ANR-EPIBACTIN)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-17-CE12-0007,EpiBactIn,Modifications epigenomiques induites par l'interaction hote-bacteries(2017), Institut Pasteur [Paris] (IP), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hamon, Melanie, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Modifications epigenomiques induites par l'interaction hote-bacteries - - EpiBactIn2017 - ANR-17-CE12-0007 - AAPG2017 - VALID
Subjects: Cytoplasm, HISTONE DEACETYLASE, [SDV]Life Sciences [q-bio], PROTEIN, lcsh:Medicine, Sirtuin 2, 0302 clinical medicine, MESH: Sirtuin 2, Medicine and Health Sciences, lcsh:Science, 0303 health sciences, SIRT2 DEACETYLASE, Multidisciplinary, biology, Chemistry, LOCALIZATION, Acetylation, Cell cycle, Cell biology, Chromatin, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Sirtuin, MESH: Acetylation, MESH: Cell Nucleus, ACETYLATION, Active Transport, Cell Nucleus, Importin, MESH: Active Transport, Cell Nucleus, Karyopherins, SIRT2, SEQUENCE, Article, 03 medical and health sciences, Humans, 030304 developmental biology, Cell Nucleus, Protein translocation, MESH: Humans, IDENTIFICATION, Mass spectrometry, MUTATIONS, MESH: Cytoplasm, lcsh:R, MESH: Karyopherins, SIGNAL, MESH: HeLa Cells, biology.protein, lcsh:Q, Histone deacetylase, Nuclear transport, HeLa Cells
Abstract: We would like to acknowledge and thank Pascale Cossart for her valuable insight and support throughout the project and for her contribution towards the acquisition of financial support. We also thank Michael G. Connor for his help in the quantification and analysis of microscopy data.; International audience; The NAD-dependent deacetylase Sirtuin-2 (SIRT2) functions in diverse cellular processes including the cell cycle, metabolism, and has important roles in tumorigenesis and bacterial infection. SIRT2 predominantly resides in the cytoplasm but can also function in the nucleus. Consequently, SIRT2 localisation and its interacting partners may greatly impact its function and need to be defined more clearly. In this study we used mass spectrometry to determine the interactomes of SIRT2 in whole cells and in specific cellular fractions; cytoplasm, nucleus and chromatin. Using this approach, we identified novel interacting partners of SIRT2. These included a number of proteins that function in nuclear import. We show that multiple importins interact with and contribute to the basal nuclear shuttling of SIRT2 and that one of these, IPO7 is required for SIRT2 mediated H3K18 deacetylation in response to bacterial infection. Furthermore, we reveal that the unstructured C-terminus of SIRT2 negatively regulates importin-binding and nuclear transport. This study demonstrates that SIRT2 is actively transported into the nucleus via a process regulated by its C-terminus and provides a resource of SIRT2 interacting partners.
Published: 2020
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221. Gene silencing with CRISPRi in bacteria and optimization of dCas9 expression levels

Author: Florence Depardieu, David Bikard, Biologie de Synthèse - Synthetic biology, Institut Pasteur [Paris], This work was supported by the European Research Council (ERC) under the Europe Union’s Horizon 2020 research and innovation program (grant agreement No [677823]), by the French Government’s Investissement d’Avenir program and by Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (ANR-10-LABX-62-IBEID), and by the Pasteur-Weizmann consortium., We thank F. Rousset for helpful discussion., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 677823,H2020,ERC-2015-STG,CRISPAIR(2016), and Institut Pasteur [Paris] (IP)
Subjects: Staphylococcus aureus, Small RNA, Transcription, Genetic, Genetic Vectors, Computational biology, Biology, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, dCas9, 03 medical and health sciences, Plasmid, CRISPR-Associated Protein 9, Escherichia coli, medicine, CRISPR, Gene silencing, Molecular Biology, 030304 developmental biology, Gene Editing, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, Gene knockdown, Cas9, 030302 biochemistry & molecular biology, CRISPRi, Gene Expression Regulation, Bacterial, 3. Good health, Rolling circle replication, Mutation, Knockdown, CRISPR-Cas Systems, Plasmids, RNA, Guide, Kinetoplastida
Abstract: International audience; The catalytic null mutant of the Cas9 endonuclease from the bacterial CRISPR immune system, known as dCas9, can be guided by a small RNA to bind DNA sequences of interest and block gene transcription in a strategy known as CRISPRi. This powerful gene silencing method has already been used in a large number of species and in high throughput screens. Here we provide detailed design rules, methods and novel vectors to perform CRISPRi experiments in S. aureus and in E. coli, using the well characterized dCas9 protein from S. pyogenes. In particular, we describe a vector based on plasmid pC194 which is broadly used in Firmicutes, as well as a vector based on the very broad host-range rolling circle plasmid pLZ12, reported to replicate in both Firmicutes and Proteobacteria. A potential caveat of adapting dCas9 tools to various bacterial species is that dCas9 was shown to be toxic when expressed too strongly. We describe a method to optimize the expression level of dCas9 in order to avoid toxicity while ensuring strong on-target repression activity. We demonstrate this method by optimizing a pLZ12 based vector originally developed for S. aureus so that it can work in E. coli. This article should provide all the resources required to perform CRISPRi experiments in a broad range of bacterial species.
Published: 2020
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222. Functional consequences of archaic introgression and their impact on fitness

Author: Lluis Quintana-Murci, Maxime Rotival, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), The laboratory of L.Q.-M. is supported by the Institut Pasteur, the Collège de France, the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10- LABX-62-IBEID) and 'Milieu Intérieur' (ANR-10-LABX-69-01), and the Fondation pour la Recherche Médicale (Equipe FRM DEQ20180339214)., 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), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Collège de France - Chaire Génomique humaine et évolution
Subjects: lcsh:QH426-470, Genetic Fitness, Adaptation, Biological, Introgression, Biology, Genetic Introgression, 03 medical and health sciences, 0302 clinical medicine, MESH: Genetic Fitness, MESH: Genetic Introgression, MESH: Epistasis, Genetic, Animals, Humans, MESH: Animals, lcsh:QH301-705.5, Alleles, MESH: Genome, Human, 030304 developmental biology, Neanderthals, MESH: Neanderthals, 0303 health sciences, MESH: Humans, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Genome, Human, MESH: Adaptation, Biological, MESH: Alleles, Epistasis, Genetic, MESH: Haplotypes, lcsh:Genetics, Editorial, Haplotypes, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, lcsh:Biology (General), Evolutionary biology, Epistasis, Adaptation, 030217 neurology & neurosurgery
Abstract: International audience; Anatomically modern humans started to exit Africa for the first time at least 60,000 years ago (ya). Along their journey across the globe, they encountered and admixed with other hominins that are now extinct, such as the Neanderthals or Denisovans. Given the deep divergence time between ancient hominins and modern humans, such admixture events left molecular traces in non-African populations that are still visible today in their genomes [1]. Over the past few years, there is accumulating evidence to suggest that these segments of “archaic” DNA have the potential to contribute to phenotypic differences between contemporary individuals and populations [2]. Yet, to understand the genuine contribution of archaic alleles to the genetic architecture of complex traits, it is necessary to account for the diverse selective pressures that have acted upon introgressed alleles. Here, we discuss recent findings on how natural selection—either negative or positive—has shaped the landscape of Neanderthal ancestry in the genomes of modern Eurasians, and comment on the contribution of archaic haplotypes to present-day phenotypic variation.
Published: 2020
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223. Molecular epidemiology, genetic variability and evolution of HTLV-1 with special emphasis on African genotypes

Author: Philippe V. Afonso, Antoine Gessain, Olivier Cassar, 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 work received the funding from the 'Investissement d’Avenir' as a part of the French Research Program 'Laboratoire d’Excellence' (LaBex): Integrative Biology of Emerging Infectious diseases (ANR10-LBX-62 IBEID)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Mutation rate, [SDV]Life Sciences [q-bio], viruses, Review, Simian, MESH: Africa, MESH: Genotype, 0302 clinical medicine, Genotype, MESH: Animals, MESH: Genetic Variation, MESH: Phylogeny, Phylogeny, MESH: Evolution, Molecular, Human T-lymphotropic virus 1, 0303 health sciences, Strain (biology), virus diseases, 3. Good health, MESH: Primates, Infectious Diseases, MESH: RNA, Viral, Molecular epidemiology, RNA, Viral, Simian T-lymphotropic virus 1, Primates, lcsh:Immunologic diseases. Allergy, MESH: Mutation, MESH: Simian T-lymphotropic virus 1, Evolution, 030231 tropical medicine, Genotypes, Biology, Virus, Evolution, Molecular, 03 medical and health sciences, Virology, MESH: HTLV-I Infections, Animals, Humans, MESH: Molecular Epidemiology, Genetic variability, 030304 developmental biology, Genetic diversity, MESH: Human T-lymphotropic virus 1, MESH: Humans, Genetic Variation, biology.organism_classification, HTLV-I Infections, Evolutionary biology, HTLV-1, Mutation, Africa, lcsh:RC581-607
Abstract: Human T cell leukemia virus (HTLV-1) is an oncoretrovirus that infects at least 10 million people worldwide. HTLV-1 exhibits a remarkable genetic stability, however, viral strains have been classified in several genotypes and subgroups, which often mirror the geographic origin of the viral strain. The Cosmopolitan genotype HTLV-1a, can be subdivided into geographically related subgroups, e.g. Transcontinental (a-TC), Japanese (a-Jpn), West-African (a-WA), North-African (a-NA), and Senegalese (a-Sen). Within each subgroup, the genetic diversity is low. Genotype HTLV-1b is found in Central Africa; it is the major genotype in Gabon, Cameroon and Democratic Republic of Congo. While strains from the HTLV-1d genotype represent only a few percent of the strains present in Central African countries, genotypes -e, -f, and -g have been only reported sporadically in particular in Cameroon Gabon, and Central African Republic. HTLV-1c genotype, which is found exclusively in Australo-Melanesia, is the most divergent genotype. This reflects an ancient speciation, with a long period of isolation of the infected populations in the different islands of this region (Australia, Papua New Guinea, Solomon Islands and Vanuatu archipelago). Until now, no viral genotype or subgroup is associated with a specific HTLV-1-associated disease. HTLV-1 originates from a simian reservoir (STLV-1); it derives from interspecies zoonotic transmission from non-human primates to humans (ancient or recent). In this review, we describe the genetic diversity of HTLV-1, and analyze the molecular mechanisms that are at play in HTLV-1 evolution. Similar to other retroviruses, HTLV-1 evolves either through accumulation of point mutations or recombination. Molecular studies point to a fairly low evolution rate of HTLV-1 (between 5.6E−7 and 1.5E−6 substitutions/site/year), supposedly because the virus persists within the host via clonal expansion (instead of new infectious cycles that use reverse transcriptase).
Published: 2019
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224. FHL1 is a major host factor for chikungunya virus infection

Author: Cécile Doyen, Thérèse Couderc, Alexis Brugier, R. Juntas-Morales, Philippe Roingeard, Rabah Ben Yaou, Julien Burlaud-Gaillard, Etienne Simon-Loriere, Mohamed Lamine Hafirassou, Sophia Rafasse, Vasiliya Kril, Pierre-Olivier Vidalain, Laura Pezzi, Gisèle Bonne, Lucie Gueneau, Xavier de Lamballerie, Marc Lecuit, Laurent Meertens, Anne Bertrand-Legout, Beate M. Kümmerer, Ali Amara, Lucie Bonnet-Madin, Thibaud Goupil, Constance Delaugerre, Athena Labeau, Monsef Benkirane, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Virology [Bonn, Germany], University of Bonn Medical Centre, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Equipe Chimie et Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5), Génomique virale et vaccination, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This study received funding from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (ANR-10-LABX-62-IBEID), the ‘Investissements d’Avenir’ program (ANR-10-IHUB-0002, ANR-15-CE15-00029 ZIKAHOST and the INCEPTION program ANR-16-CONV-0005), Institut Pasteur, Inserm and European Research Council. Viruses were provided by the Europe and Virus Archive, which has received funding from the EU Horizon 2020 research and innovation program under grant agreement 653316. The authors thank the EA7310, Laboratoire de Virologie, Université de Corse-Inserm for funding the doctoral position of L.P., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-17-CE15-0029,ZIKAHOST,LES FACTEURS DE L'HÔTE ASSOCIÉS À LA NEUROPATHOGÉNICITÉ DU VIRUS ZIKA(2017), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Institut National de la Santé et de la Recherche Médicale (INSERM)-Collège de France (CdF (institution))-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Myologie, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), BUISINE, Soline, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, LES FACTEURS DE L'HÔTE ASSOCIÉS À LA NEUROPATHOGÉNICITÉ DU VIRUS ZIKA - - ZIKAHOST2017 - ANR-17-CE15-0029 - AAPG2017 - VALID, and Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID
Subjects: Male, Permissiveness, viruses, Viral pathogenesis, Muscle Proteins, Host-Derived Cellular Factors, Alphavirus, Viral Nonstructural Proteins, Virus Replication, medicine.disease_cause, Virus, Myoblasts, Mice, 03 medical and health sciences, medicine, Animals, Humans, O'nyong-nyong Virus, Chikungunya, Cells, Cultured, 030304 developmental biology, Host factor, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Multidisciplinary, biology, 030306 microbiology, Intracellular Signaling Peptides and Proteins, virus diseases, Fibroblasts, LIM Domain Proteins, biology.organism_classification, Virology, FHL1, 3. Good health, HEK293 Cells, Viral replication, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chikungunya Fever, RNA, Viral, Female, Chikungunya virus, Protein Binding
Abstract: Chikungunya virus (CHIKV) is a re-emerging alphavirus that is transmitted to humans by mosquito bites and causes musculoskeletal and joint pain1,2. Despite intensive investigations, the human cellular factors that are critical for CHIKV infection remain unknown, hampering the understanding of viral pathogenesis and the development of anti-CHIKV therapies. Here we identified the four-and-a-half LIM domain protein 1 (FHL1)3 as a host factor that is required for CHIKV permissiveness and pathogenesis in humans and mice. Ablation of FHL1 expression results in the inhibition of infection by several CHIKV strains and o’nyong-nyong virus, but not by other alphaviruses and flaviviruses. Conversely, expression of FHL1 promotes CHIKV infection in cells that do not normally express it. FHL1 interacts directly with the hypervariable domain of the nsP3 protein of CHIKV and is essential for the replication of viral RNA. FHL1 is highly expressed in CHIKV-target cells and is particularly abundant in muscles3,4. Dermal fibroblasts and muscle cells derived from patients with Emery–Dreifuss muscular dystrophy that lack functional FHL15 are resistant to CHIKV infection. Furthermore, CHIKV infection is undetectable in Fhl1-knockout mice. Overall, this study shows that FHL1 is a key factor expressed by the host that enables CHIKV infection and identifies the interaction between nsP3 and FHL1 as a promising target for the development of anti-CHIKV therapies. FHL1 is a key factor expressed by humans and mice that is required for chikungunya virus infection and is therefore a promising target for the development of therapies against chikungunya virus.
Published: 2019
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225. Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus

Author: Donal Bisanzio, Thomas W. Scott, G. R. William Wint, T. Alex Perkins, Nicole Davis Weaver, Lucas Earl, Laurie B. Marczak, Erik Wetter, Hongjie Yu, Shengjie Lai, Dingdong Yi, Simon I. Hay, Wim Van Bortel, Cedric Marsboom, Francis Schaffner, Giovanini E. Coelho, David M. Pigott, Jane P. Messina, Xin Lu, Robert C. Reiner, Linus Bengtsson, Andrew J. Tatem, David L. Smith, Chester G. Moore, Shreya Shirude, Qiyong Liu, Peter A. Jones, Kimberly J. Johnson, Roberta G. Carvalho, John S. Brownstein, Moritz U. G. Kraemer, Oliver J. Brady, Nuno R. Faria, Louis Lambrechts, Nick Golding, Marius Gilbert, Heinrich H. Nax, Guy Hendrickx, Oliver G. Pybus, Simon Cauchemez, Catherine Linard, University of Oxford [Oxford], Boston Children's Hospital, Harvard Medical School [Boston] (HMS), University of Washington [Seattle], London School of Hygiene and Tropical Medicine (LSHTM), Université libre de Bruxelles (ULB), Fonds National de la Recherche Scientifique [Bruxelles] (FNRS), Harvard University [Cambridge], University of Nottingham, UK (UON), Eck Institute for Global Health, University of Notre Dame [Indiana] (UND), Fudan University [Shanghai], University of Southampton, Flowminder Foundation, Central South University [Changsha], National University of Defense Technology [China], Southwestern University of Finance and Economics [Chengdu, China], Waen Associates Ltd, Pan American Health Organization [Washington] (PAHO), Ministry of Health [Brasília, Brazil], European Centre for Disease Prevention and Control (ECDC), Institute of Tropical Medicine [Antwerp] (ITM), Egis Avia (FRANCE), Francis Schaffner Consultancy, Colorado State University [Fort Collins] (CSU), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Karolinska Institutet [Stockholm], Stockholm School of Economics (SSE), Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Namur [Namur] (UNamur), University of California [Davis] (UC Davis), University of California, Chinese Center for Disease Control and Prevention, Shandong University, University of Melbourne, The authors thank S. Ray for providing comments during the revision process. M.U.G.K. acknowledges funding from the Society in Science, The Branco Weiss Fellowship, administered by the ETH Zurich. M.U.G.K. also acknowledges funding from the Training Grant from the National Institute of Child Health and Human Development (T32HD040128). M.U.G.K., S.I.H., J.P.M., N.G., O.J.B. and G.R.W.W. acknowledge funding from the International Research Consortium on Dengue Risk Assessment Management and Surveillance (IDAMS, European Commission 7th Framework Programme no. 21893). O.B.J. was funded by a Sir Henry Wellcome Fellowship funded by the Wellcome Trust (grant number 206471/Z/17/Z) and a grant from the Bill and Melinda Gates Foundation (OP1183567). S.I.H. received a grant from the Research for Health in Humanitarian Crises (R2HC) Programme, managed by Enhancing Learning and Research for Humanitarian Assistance (ELRHA, no. 13468), which also supported M.U.G.K. and N.G. The R2HC programme aims to improve health outcomes by strengthening the evidence base for public health interventions in humanitarian crises. The £8 million R2HC programme is funded equally by the Wellcome Trust and Department of International Development (DFiD), with ELRHA overseeing the programme’s execution and management. S.I.H. was also funded by a Senior Research Fellowship from the Wellcome Trust (no. 95066) and grants from the Bill & Melinda Gates Foundation (OPP1106023, OPP1093011, OPP1132415 and OPP1159934). This study was made possible by the support of the American people through the US Agency for International Development Emerging Pandemic Threats Program-2 PREDICT-2 (Cooperative Agreement number AID-OAA-A-14-00102), which also supported M.U.G.K. J.S.B. is supported by the National Library of Medicine of the National Institutes of Health (R01LM010812 and R01LM011965), which also supports M.U.G.K. D.L.S. is funded by the National Institutes of Health and National Institute of Allergy and Infectious Diseases (no. U10AI089674). H.H.N. was funded by the European Commission through the European Research Council Advanced Investigator Grant ‘Momentum’ 324247. L.L. received funding from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID), the French Agence Nationale de la Recherche (grant ANR-16-CE35-0004), the City of Paris Emergence(s) programme in Biomedical Research, and the European Union’s Horizon 2020 research and innovation programme under ZikaPLAN grant agreement No. 734584. S.C. received funding from the AXA Research Fund, the Investissement d’Avenir program, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program (Grant ANR-10-LABX-62-IBEID), the Models of Infectious Disease Agent Study of the National Institute of General Medical Sciences, the INCEPTION project (PIA/ANR-16-CONV-0005), and the European Union’s Horizon 2020 research and innovation programme under ZIKAlliance grant agreement No 734548. N.G. is supported by a University of Melbourne McKenzie fellowship. W.V.B., G.H. and F.S. acknowledge funding from VBORNET and VectorNet, an ECDC and EFSA-funded project (no. ECDC/09/018 and OC/EFSA/AHAW/2013/02), and thank all contributing VBORNET and VectorNet experts for data sharing. T.W.S., R.C.R. and L.L. received funding from the National Institutes of Health Program Project grant (no. P01 AI098670). X.L. is supported by the Natural Science Foundation of China (71771213, 71522014, 71725001, 91846301 and 71790615). This work was also partially supported by the European Union’s Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement no. 734548., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CE35-0004,MOSQUIBIOTA,Contribution de la diversité bactérienne intestinale à la capacité vectorielle d'Aedes aegypti(2016), European Project: 734548,ZIKAlliance(2016), European Project: 324247,EC:FP7:ERC,ERC-2012-ADG_20120411,MOMENTUM(2013), European Project: 281803,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,IDAMS(2011), University of Oxford, Harvard University, European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and University of California (UC)
Subjects: Microbiology (medical), Microbiologie et protistologie [parasitologie hum. et anim.], Aedes albopictus, Arbovirus Infections, Immunology, Aedes aegypti, medicine.disease_cause, Applied Microbiology and Biotechnology, Arbovirus, Microbiology, Article, Dengue fever, Zika virus, 03 medical and health sciences, Genetics, medicine, Chikungunya, 030304 developmental biology, Aedes, 0303 health sciences, biology, 030306 microbiology, Ecology, virus diseases, Cell Biology, biology.organism_classification, medicine.disease, 3. Good health, Microbiologie et protistologie [entomologie,phytoparasitolog.], Geography, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Infectious diseases
Abstract: The global population at risk from mosquito-borne diseases—including dengue, yellow fever, chikungunya and Zika—is expanding in concert with changes in the distribution of two key vectors: Aedes aegypti and Aedes albopictus. The distribution of these species is largely driven by both human movement and the presence of suitable climate. Using statistical mapping techniques, we show that human movement patterns explain the spread of both species in Europe and the United States following their introduction. We find that the spread of Ae. aegypti is characterized by long distance importations, while Ae. albopictus has expanded more along the fringes of its distribution. We describe these processes and predict the future distributions of both species in response to accelerating urbanization, connectivity and climate change. Global surveillance and control efforts that aim to mitigate the spread of chikungunya, dengue, yellow fever and Zika viruses must consider the so far unabated spread of these mosquitos. Our maps and predictions offer an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally., 0, SCOPUS: ar.j, SCOPUS: er.j, info:eu-repo/semantics/published
Published: 2019
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226. SME-4-producing Serratia marcescens from Argentina belonging to clade 2 of the S. marcescens phylogeny

Author: Marcela Nastro, Angela Famiglietti, Philippe Glaser, Carlos Hernán Rodríguez, Rafael Patiño-Navarrete, Laura Dabos, Thierry Naas, Structure, Dynamique, Fonction Et Expression Des Beta-Lactamases À Large Spectre, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11)-Université Paris-Sud - Paris 11 (UP11)-Centre National de Référence de la Résistance aux Antibiotiques (CNR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Université Paris-Sud - Paris 11 (UP11)-Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Laboratorio de Bacteriología Clínica [Buenos Aires], Facultad de Farmacia y Bioquímica [Buenos Aires] (FFYB), Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA), Universidad de Buenos Aires [Buenos Aires] (UBA), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre National de Référence Associé de la Résistance aux Antibiotiques [Hôpital Bicêtre AP-HP] (CNRARA/Service de Microbiologie), This work was supported by the Assistance Publique – Hôpitaux de Paris (AP-HP), the University Paris-Sud, the LabExs Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT) and Integrative Biology of Emerging Infectious Diseases (IBEID) supported by grants from the French National Research Agency (ANR-10-LABX-33), and by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) DesInMBL (ANR-14-JAMR-002), and by DIM Malinf, Ile deFrance, for L. D.’s PhD fellowship., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-JAMR-0002,DesInMBL,Structure-guided design of pan inhibitors of metallo-ß-lactamases(2014), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Sud Orsay-Centre National de la Recherche Scientifique (CNRS), and Centre National de Référence Associé de la Résistance aux Antibiotiques
Subjects: Male, 0301 basic medicine, Microbiology (medical), Imipenem, Genomic Islands, Genotype, 030106 microbiology, Argentina, Microbial Sensitivity Tests, Genome, beta-Lactamases, Serratia Infections, 03 medical and health sciences, 0302 clinical medicine, Bacterial Proteins, Phylogenetics, Genomic island, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Clade, Phylogeny, Serratia marcescens, Pharmacology, Genetics, Whole genome sequencing, Whole Genome Sequencing, biology, Phylogenetic tree, Computational Biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Middle Aged, biology.organism_classification, Carbapenem-Resistant Enterobacteriaceae, Infectious Diseases, Genome, Bacterial, medicine.drug
Abstract: Background SME carbapenemases are increasingly reported, especially from North and South America. Here, we describe an SME-4-producing Serratia marcescens (SME-Sm) clinical isolate from Argentina and compare its genome with other SME-Sm and Sm isolates recovered from public databases. Methods Sm isolates were characterized by WGS using Illumina technology, susceptibility testing and MIC determination. Carbapenemase activity was revealed by biochemical tests based on imipenem hydrolysis. A whole-genome phylogeny was estimated for all the Sm isolates retrieved from public databases with kSNP3 and a whole-genome phylogenetic analysis based on non-recombinant core SNPs was inferred for Sm complete genomes and for those encoding any blaSME variants. Results Sm163 was resistant to amoxicillin, temocillin, aztreonam and carbapenems, remaining susceptible to extended-spectrum cephalosporins. WGS analysis of Sm163 revealed a genome of 5139329 bp and a chromosomally encoded blaSME-4 carbapenemase gene located on a genomic island closely related to SmarGI1-1 of Sm N11-02820. Comparison of the Sm genomes revealed that the 14 SME-Sm isolates possess this genomic island inserted at the same loci, that 13/14 belong to clade 1 and that 11/14 form a well-defined subcluster of cluster I of Sm clade 1, while Sm163 belongs to clade 2, suggesting that an SME-encoding genomic island may have been transferred between isolates from different clades. Conclusions To the best of our knowledge this is the first report of an SME-4-encoding Sm from Argentina. The blaSME-4 gene is located on a SmarGI1-1-like genomic island. The genome of Sm163 belongs to clade 2, unlike all the other SME-Sm isolates, which belong to clade 1.
Published: 2019
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227. Duration of BA.5 neutralization in sera and nasal swabs from SARS-CoV-2 vaccinated individuals, with or without omicron breakthrough infection

Author: Delphine Planas, Isabelle Staropoli, Françoise Porot, Florence Guivel-Benhassine, Lynda Handala, Mathieu Prot, William-Henry Bolland, Julien Puech, Hélène Péré, David Veyer, Aymeric Sève, null Etienne-Simon-Lorière, Timothée Bruel, Thierry Prazuck, Karl Stefic, Laurent Hocqueloux, Olivier Schwartz, 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), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-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), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), 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)-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 Hospitalier Régional d'Orléans (CHRO), Work in O.S.'s laboratory 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, ANR Coronamito, and IDISCOVR, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant no. ANR-10-LABX-62-IBEID), HERA european funding and the NIH PICREID (grant no U01AI151758)., The authors thank A. Fontanet for critical reading of the manuscript, the patients who participated to this study, members of the Virus and Immunity Unit and other teams for discussion and help, N. Aulner and the staff at the UtechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis, and F. Peira, V. Legros, and L. Courtellemont for their help with the cohorts., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020)
Subjects: variants, MESH: Humans, Breakthrough Infections, IgG, Omicron, SARS-CoV-2, MESH: Breakthrough Infections, [SDV]Life Sciences [q-bio], Translation to patients, COVID-19, General Medicine, neutralization, Antibodies, Neutralizing, MESH: Antibodies, Neutralizing, vaccine, mucosal immunity, MESH: COVID-19, Humans, breakthrough, MESH: SARS-CoV-2, MESH: BNT162 Vaccine, IgA, BNT162 Vaccine, BA.5
Abstract: Since early 2022, Omicron BA.1 has been eclipsed by BA.2, which was in turn outcompeted by BA.5, which displays enhanced antibody escape properties.Here, we evaluated the duration of the neutralizing antibody (Nab) response, up to 18 months after Pfizer BNT162b2 vaccination, in individuals with or without BA.1/BA.2 breakthrough infection. We measured neutralization of the ancestral D614G lineage, Delta, and Omicron BA.1, BA.2, and BA.5 variants in 300 sera and 35 nasal swabs from 27 individuals.Upon vaccination, serum Nab titers were decreased by 10-, 15-, and 25-fold for BA.1, BA.2, and BA.5, respectively, compared with D614G. We estimated that, after boosting, the duration of neutralization was markedly shortened from 11.5 months with D614G to 5.5 months with BA.5. After breakthrough, we observed a sharp increase of Nabs against Omicron subvariants, followed by a plateau and a slow decline after 5-6 months. In nasal swabs, infection, but not vaccination, triggered a strong immunoglobulin A (IgA) response and a detectable Omicron-neutralizing activity.BA.5 spread is partly due to abbreviated vaccine efficacy, particularly in individuals who were not infected with previous Omicron variants.Work in O.S.'s laboratory 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, ANR Coronamito, and IDISCOVR, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant no. ANR-10-LABX-62-IBEID), HERA european funding and the NIH PICREID (grant no U01AI151758).
Published: 2022
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228. SHERLOCK4HAT: A CRISPR-based tool kit for diagnosis of Human African Trypanosomiasis

Author: Núria Sima, Annick Dujeancourt-Henry, Blanca Liliana Perlaza, Marie-Noelle Ungeheuer, Brice Rotureau, Lucy Glover, Biologie moléculaire des Trypanosomes - Trypanosome Molecular Biology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Biologie cellulaire des Trypanosomes - Trypanosome Cell Biology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur de Guinée, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur (PTR-175 SHERLOCK4HAT), French Government's Investissement d’Avenir program Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (LabEx IBEID), and Agence Nationale pour la Recherche (ANR-PRC 2021 SherPa)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-21-CE17-0022,SherPa,Développement d'une plateforme SHERLOCK pour la détection polyvalente des parasites trypanosomatidés.(2021)
Subjects: Trypanosomiasis, African, [SDV]Life Sciences [q-bio], Trypanosoma brucei gambiense, HAT, Humans, Animals, Diagnostic, Trypanosoma brucei, General Medicine, General Biochemistry, Genetics and Molecular Biology, SHERLOCK
Abstract: To achieve elimination of Human African Trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense (gHAT), the development of highly sensitive diagnostics is needed. We have developed a CRISPR based diagnostic for HAT using SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) that is readily adaptable to a field-based setting.We adapted SHERLOCK for the detection of T. brucei species. We targeted 7SLRNA, TgSGP and SRA genes and tested SHERLOCK against RNA from blood, buffy coat, dried blood spots (DBS), and clinical samples.The pan-Trypanozoon 7SLRNA and T. b. gambiense-specific TgSGP SHERLOCK assays had a sensitivity of 0.1 parasite/μL and a limit of detection 100 molecules/μL. T. b. rhodesiense-specific SRA had a sensitivity of 0.1 parasite/μL and a limit of detection of 10 molecules/μL. TgSGP SHERLOCK and SRA SHERLOCK detected 100% of the field isolated strains. Using clinical specimens from the WHO HAT cryobank, the 7SLRNA SHERLOCK detected trypanosomes in gHAT samples with 56.1%, 95% CI [46.25-65.53] sensitivity and 98.4%, 95% CI [91.41-99.92] specificity, and rHAT samples with 100%, 95% CI [83.18-100] sensitivity and 94.1%, 95% CI [80.91-98.95] specificity. The species-specific TgSGP and SRA SHERLOCK discriminated between the gambiense/rhodesiense HAT infections with 100% accuracy.The 7SLRNA, TgSGP and SRA SHERLOCK discriminate between gHAT and rHAT infections, and could be used for epidemiological surveillance and diagnosis of HAT in the field after further technical development.Institut Pasteur (PTR-175 SHERLOCK4HAT), French Government's Investissement d'Avenir program Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (LabEx IBEID), and Agence Nationale pour la Recherche (ANR-PRC 2021 SherPa).
Published: 2022
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229. Enhanced mosquito vectorial capacity underlies the Cape Verde Zika epidemic

Author: Noah H. Rose, Stéphanie Dabo, Silvânia da Veiga Leal, Massamba Sylla, Cheikh T. Diagne, Oumar Faye, Ousmane Faye, Amadou A. Sall, Carolyn S. McBride, Louis Lambrechts, Princeton University, Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Instituto Nacional de Saúde Pública [Cabo Verde] (INSP), Université du Sine Saloum El-Hadj Ibrahima NIASS (USSEIN), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), This work was supported by the European Union’s Horizon 2020 research and innovation programme under ZikaPLAN grant agreement no. 734584 (to LL), Agence Nationale de la Recherche (grant ANR-18-CE35-0003-01 to LL), the French Government’s Investissement d’Avenir program Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID to LL), and the US National Institutes of Health (grant NIDCD R00-DC012069 to CSM). NHR was supported by a Helen Hay Whitney Postdoctoral Fellowship. CSM is a New York Stem Cell Foundation – Robertson Investigator., ANR-18-CE35-0003,BAKOUMBA,Dissection de la base génétique d'un phénotype naturel de résistance à la dengue chez le moustique Aedes aegypti(2018), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and European Project: no. 734584
Subjects: MESH: Humans, General Immunology and Microbiology, Zika Virus Infection, General Neuroscience, MESH: Zika Virus, Zika Virus, Mosquito Vectors, MESH: Aedes, MESH: Cabo Verde, General Biochemistry, Genetics and Molecular Biology, MESH: Zika Virus Infection, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Aedes, Cabo Verde, Animals, Humans, MESH: Animals, MESH: Saliva, MESH: Mosquito Vectors, Saliva, Epidemics, General Agricultural and Biological Sciences, MESH: Epidemics
Abstract: The explosive emergence of Zika virus (ZIKV) across the Pacific and Americas since 2007 was associated with hundreds of thousands of human cases and severe outcomes, including congenital microcephaly caused by ZIKV infection during pregnancy. Although ZIKV was first isolated in Uganda, Africa has so far been exempt from large-scale ZIKV epidemics, despite widespread susceptibility among African human populations. A possible explanation for this pattern is natural variation among populations of the primary vector of ZIKV, the mosquito Aedes aegypti. Globally invasive populations of Ae. aegypti outside of Africa are considered effective ZIKV vectors because they are human specialists with high intrinsic ZIKV susceptibility, whereas African populations of Ae. aegypti across the species’ native range are predominantly generalists with low intrinsic ZIKV susceptibility, making them less likely to spread viruses in the human population. We test this idea by studying a notable exception to the patterns observed across most of Africa: Cape Verde experienced a large ZIKV outbreak in 2015 to 2016. We find that local Ae. aegypti in Cape Verde have substantial human-specialist ancestry, show a robust behavioral preference for human hosts, and exhibit increased susceptibility to ZIKV infection, consistent with a key role for variation among mosquito populations in ZIKV epidemiology. These findings suggest that similar human-specialist populations of Ae. aegypti in the nearby Sahel region of West Africa, which may be expanding in response to rapid urbanization, could serve as effective vectors for ZIKV in the future.
Published: 2022
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230. Sporadic occurrence of recent selective sweeps from standing variation in humans as revealed by an approximate Bayesian computation approach

Author: Lluis Quintana-Murci, Guillaume Laval, Etienne Patin, Pierre Boutillier, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Harvard Medical School [Boston] (HMS), This work was supported by the Agence Nationale de la Recherche (ANR) grant 'DEMOCHIPS' ANR-12-BSV7‐0012. The Human Evolutionary Genetics laboratory is supported by the Institut Pasteur, the Collège de France, the CNRS, the Fondation Allianz-Institut de France, and the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (ANR-10-LABX-62-IBEID) and ‘Milieu Intérieur’ (ANR-10-LABX-69-01)., 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), and ANR-12-BSV7-0012,demochips,Inférence de l'histoire démographique à partie des grands jeux de données de polymorphisme A.D.N.(2012)
Subjects: Variation (game tree), Biology, Divergence, 03 medical and health sciences, 0302 clinical medicine, selective sweeps, human adaptation, Genetics, Animals, Humans, Computer Simulation, Selection, Genetic, Selection (genetic algorithm), 030304 developmental biology, Local adaptation, Investigation, 0303 health sciences, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Sporadic occurrence, Computational Biology, Genetic Variation, Bayes Theorem, Adaptation, Physiological, Biological Evolution, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Biological Variation, Population, Evolutionary biology, Approximate Bayesian computation, Adaptation, ABC, 030217 neurology & neurosurgery, Genetic adaptation
Abstract: During their dispersals over the last 100,000 years, modern humans have been exposed to a large variety of environments, resulting in genetic adaptation. While genome-wide scans for the footprints of positive Darwinian selection have increased knowledge of genes and functions potentially involved in human local adaptation, they have globally produced evidence of a limited contribution of selective sweeps in humans. Conversely, studies based on machine learning algorithms suggest that recent sweeps from standing variation are widespread in humans, an observation that has been recently questioned. Here, we sought to formally quantify the number of recent selective sweeps in humans, by leveraging approximate Bayesian computation and whole-genome sequence data. Our computer simulations revealed suitable ABC estimations, regardless of the frequency of the selected alleles at the onset of selection and the completion of sweeps. Under a model of recent selection from standing variation, we inferred that an average of 68 (from 56 to 79) and 140 (from 94 to 198) sweeps occurred over the last 100,000 years of human history, in African and Eurasian populations, respectively. The former estimation is compatible with human adaptation rates estimated since divergence with chimps, and reveals numbers of sweeps per generation per site in the range of values estimated in Drosophila. Our results confirm the rarity of selective sweeps in humans and show a low contribution of sweeps from standing variation to recent human adaptation.
Published: 2021
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231. SARS-CoV-2 Alpha, Beta, and Delta variants display enhanced Spike-mediated syncytia formation

Author: Mathieu Hubert, Jérémy Dufloo, Rémy Robinot, Hugo Mouquet, Olivier Schwartz, Ludivine Grzelak, Nell Saunders, Elodie Bishop, Françoise Porrot, Delphine Planas, Maaran Michael Rajah, Julian Buchrieser, Lisa A. Chakrabarti, Marija Zivaljic, Alice Bongers, Stacy Gellenoncourt, Florence Guivel-Benhassine, Cyril Planchais, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Sorbonne Université (SU), Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC), Institut Pasteur [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ecole doctorale Cerveau Cognition et Comportement [Paris] (ED 158 - 3C), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Fondation Pour la Recherche Médicale (FRM), Labex IBEID (ANR-10-LABX62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, ANR CoronaMito AAP RA-COVID-19 V14, and IDISCOVR. Work in UPBI is funded by grant ANR-10-INSB-04-01 and Région Ile-de-France program DIM1-Health. MMR and MZ are supported by the Pasteur-Paris University (PPU) International Doctoral Program. MMR is also supported by Institut Pasteur Department of Virology 'Bourse de Soudure' fellowship. DP is supported by the Vaccine Research Institute. LG is supported by the French Ministry of Higher Education, Research and Innovation. EB is supported by the Medecine-Sciences ENS-PSL Program. HM laboratory is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69- 01), the INSERM, REACTing, EU (RECOVER), and Fondation de France (#00106077) grants., We thank members of the Virus and Immunity Unit for helpful discussions, Dr. Nicoletta Casartelli for her critical reading of the manuscript, and Nathalie Aulner and the UtechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis support., 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-21-CO14-0007,CoronaMito,Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale(2021), 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), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris] (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ziani, Isma, 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, Protéomique du SARS-CoV-2 - - PROTEO-SARS-CoV-22020 - ANR-20-COVI-0059 - COVID-19 - VALID, Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale - - CoronaMito2021 - ANR-21-CO14-0007 - COVID-19 - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, and Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID
Subjects: fusion, coronavirus, MESH: Spike Glycoprotein, Coronavirus, MESH: Angiotensin-Converting Enzyme 2, medicine.disease_cause, Virus Replication, Giant Cells, SARS‐CoV‐2, MESH: Antibodies, Monoclonal, MESH: Giant Cells, MESH: Chlorocebus aethiops, Chlorocebus aethiops, MESH: Animals, Receptor, Coronavirus, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Syncytium, Strain (chemistry), General Neuroscience, Antibodies, Monoclonal, Articles, Transmembrane protein, Microbiology, Virology & Host Pathogen Interaction, Cell biology, MESH: HEK293 Cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Spike Glycoprotein, Coronavirus, MESH: Caco-2 Cells, Angiotensin-Converting Enzyme 2, MESH: Mutation, medicine.drug_class, Immunology, Alpha (ethology), MESH: Vero Cells, Biology, Monoclonal antibody, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, medicine, Animals, Humans, MESH: SARS-CoV-2, Beta (finance), syncytia, Molecular Biology, Vero Cells, MESH: Humans, General Immunology and Microbiology, SARS-CoV-2, MESH: Virus Replication, spike, MESH: Cell Line, HEK293 Cells, Mutation, Caco-2 Cells
Abstract: Severe COVID‐19 is characterized by lung abnormalities, including the presence of syncytial pneumocytes. Syncytia form when SARS‐CoV‐2 spike protein expressed on the surface of infected cells interacts with the ACE2 receptor on neighboring cells. The syncytia forming potential of spike variant proteins remain poorly characterized. Here, we first assessed Alpha (B.1.1.7) and Beta (B.1.351) spread and fusion in cell cultures, compared with the ancestral D614G strain. Alpha and Beta replicated similarly to D614G strain in Vero, Caco‐2, Calu‐3, and primary airway cells. However, Alpha and Beta formed larger and more numerous syncytia. Variant spike proteins displayed higher ACE2 affinity compared with D614G. Alpha, Beta, and D614G fusion was similarly inhibited by interferon‐induced transmembrane proteins (IFITMs). Individual mutations present in Alpha and Beta spikes modified fusogenicity, binding to ACE2 or recognition by monoclonal antibodies. We further show that Delta spike also triggers faster fusion relative to D614G. Thus, SARS‐CoV‐2 emerging variants display enhanced syncytia formation., Spike protein mutations expressed by emerging SARS‐CoV‐2 variants‐of‐concern differentially affect host cell‐to‐cell fusion, ACE2 receptor binding, and antibody escape.
Published: 2021
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232. Histone H3 deacetylation promotes host cell viability for efficient infection by Listeria monocytogenes

Author: Eldridge, Matthew, Hamon, Mélanie, Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris] (IP), MJGE is supported by a fellowship from the French Government’s Investissement d’Avenir program, the Laboratoire d’Excellence ‘‘Integrative Biology of Emerging Infectious Diseases’’ Agence Nationale de la Recherche (ANR): ANR-10-LABX-62-EIBID. Work in the M.A.H. laboratory received financial support from the Institut Pasteur, the Agence Nationale de la Recherche (ANR: https://anr.fr/):ANR-17-CE12-0007, the Fondation pour la Recherche Médicale (FRM: https://www.frm.org/): EQU202003010152, the Fondation iXCore-iXLife (https://ixlife.com/) and the Pasteur-Weizmann research fund,(https://www.weizmann-france.com/)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-17-CE12-0007,EpiBactIn,Modifications epigenomiques induites par l'interaction hote-bacteries(2017)
Subjects: Cell Survival, [SDV]Life Sciences [q-bio], Cultured tumor cells, Pathology and Laboratory Medicine, Transfection, Microbiology, Biochemistry, Histones, Sirtuin 3, Virology, Medicine and Health Sciences, Genetics, Animals, Humans, Listeriosis, HeLa cells, Non-coding RNA, Molecular Biology Techniques, Microbial Pathogens, Molecular Biology, Chromosome Biology, Host Cells, Biology and Life Sciences, DNA, Cell Biology, Small interfering RNA, Listeria Monocytogenes, Cell cultures, Chromatin, Bacterial Pathogens, Gene regulation, Nucleic acids, Research and analysis methods, Intracellular Pathogens, Medical Microbiology, Host-Pathogen Interactions, DNA damage, Cell lines, RNA, Epigenetics, Gene expression, Pathogens, Biological cultures, Viral Transmission and Infection, Research Article
Abstract: For many intracellular bacterial pathogens manipulating host cell survival is essential for maintaining their replicative niche, and is a common strategy used to promote infection. The bacterial pathogen Listeria monocytogenes is well known to hijack host machinery for its own benefit, such as targeting the host histone H3 for modification by SIRT2. However, by what means this modification benefits infection, as well as the molecular players involved, were unknown. Here we show that SIRT2 activity supports Listeria intracellular survival by maintaining genome integrity and host cell viability. This protective effect is dependent on H3K18 deacetylation, which safeguards the host genome by counteracting infection-induced DNA damage. Mechanistically, infection causes SIRT2 to interact with the nucleic acid binding protein TDP-43 and localise to genomic R-loops, where H3K18 deacetylation occurs. This work highlights novel functions of TDP-43 and R-loops during bacterial infection and identifies the mechanism through which L. monocytogenes co-opts SIRT2 to allow efficient infection., Author summary To cause systemic disease Listeria monocytogenes assumes an intracellular lifestyle which supports its growth and dissemination during infection. In order to maintain the intracellular niche L. monocytogenes manipulates various host cell processes thereby promoting its own survival and infection. One such example is the hijacking of a host deacetylase called SIRT2 which upon infection localises to chromatin, specifically modifies lysine 18 of histone H3 and promotes intracellular bacterial growth. Here we identify how SIRT2 promotes infection. We show that SIRT2-mediated H3K18 deacetylation counteracts infection-induced DNA damage and identify the molecular complex at play. Such SIRT2 activity has a crucial role in promoting host cell viability during infection, allowing for better survival upon heavy intracellular bacterial burden, and resulting in enhanced infection by L. monocytogenes.
Published: 2021
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233. Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential

Author: Jeanne Chiaravalli, Marius Walter, Edward Emmott, Emma Sierecki, Stacy Gellenoncourt, Philip Brownridge, Arturas Grauslys, Andrew R. Jones, Fabrice Agou, Charles S. Craik, Marco Vignuzzi, Yann Gambin, Patrick A. Eyers, Lisa A. Chakrabarti, Eric Verdin, Leonard A. Daly, Bjoern Meyer, Dominic P. Bryne, Claire E. Eyers, Populations virales et Pathogenèse - Viral Populations and Pathogenesis, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Criblage chémogénomique et biologique (Plateforme) - Chemogenomic and Biological Screening Platform (PF-CCB), Institut Pasteur [Paris] (IP), Virus et Immunité - Virus and immunity (CNRS-UMR3569), University of Liverpool, Buck Institute for Research on Aging, University of California [San Francisco] (UC San Francisco), University of California (UC), University of New South Wales [Sydney] (UNSW), This work was supported by the Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant ANR-10-LABX-62-IBEID) to M.V. S.G. is the recipient of a MESR/Ecole Doctorale BioSPC ED562, Université de Paris fellowship. L.A.C. is supported by Institut Pasteur TASK FORCE SARS COV-2 (Tropicoro project), DIM ELICIT Region Ile-de-France, and ANRS. E.E. is supported by startup funding from the University of Liverpool, as well as a Wellcome Trust ISSF Interdisciplinary & Industry Award. E.E. is grateful for the support of GoFundMe donors for sponsoring SARS-CoV-2 research in his laboratory., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: Proteomics, MESH: Virus Internalization, viruses, medicine.medical_treatment, General Physics and Astronomy, Virus Replication, MESH: Dipeptides, MESH: RNA, Small Interfering, 2.2 Factors relating to the physical environment, MESH: COVID-19, MESH: Animals, MESH: Myosin-Light-Chain Kinase, RNA, Small Interfering, Aetiology, skin and connective tissue diseases, Lung, MESH: Protease Inhibitors, MESH: Viral Proteases, Multidisciplinary, medicine.diagnostic_test, Viral Proteases, MESH: Proteomics, Proteases, Dipeptides, src-Family Kinases, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Infection, Biotechnology, Proto-oncogene tyrosine-protein kinase Src, MESH: Antiviral Agents, MESH: Mutation, Science, Proteolysis, MESH: Proteolysis, Context (language use), Biology, Small Interfering, Antiviral Agents, Article, General Biochemistry, Genetics and Molecular Biology, Cell Line, Vaccine Related, Viral Proteins, Biodefense, medicine, Animals, Humans, Protease Inhibitors, MESH: SARS-CoV-2, Myosin-Light-Chain Kinase, MESH: Humans, Protease, SARS-CoV-2, Prevention, fungi, MESH: Virus Replication, COVID-19, MYLK, Pneumonia, General Chemistry, Virus Internalization, MESH: Viral Proteins, Virology, COVID-19 Drug Treatment, MESH: Cell Line, body regions, Emerging Infectious Diseases, Good Health and Well Being, MESH: src-Family Kinases, Viral replication, Mutation, RNA, Immunization
Abstract: SARS-CoV-2 is the causative agent behind the COVID-19 pandemic, responsible for over 170 million infections, and over 3.7 million deaths worldwide. Efforts to test, treat and vaccinate against this pathogen all benefit from an improved understanding of the basic biology of SARS-CoV-2. Both viral and cellular proteases play a crucial role in SARS-CoV-2 replication. Here, we study proteolytic cleavage of viral and cellular proteins in two cell line models of SARS-CoV-2 replication using mass spectrometry to identify protein neo-N-termini generated through protease activity. We identify previously unknown cleavage sites in multiple viral proteins, including major antigens S and N: the main targets for vaccine and antibody testing efforts. We discover significant increases in cellular cleavage events consistent with cleavage by SARS-CoV-2 main protease, and identify 14 potential high-confidence substrates of the main and papain-like proteases. We show that siRNA depletion of these cellular proteins inhibits SARS-CoV-2 replication, and that drugs targeting two of these proteins: the tyrosine kinase SRC and Ser/Thr kinase MYLK, show a dose-dependent reduction in SARS-CoV-2 titres. Overall, our study provides a powerful resource to understand proteolysis in the context of viral infection, and to inform the development of targeted strategies to inhibit SARS-CoV-2 and treat COVID-19., During SARS-CoV-2 replication, viral and cellular proteases play crucial roles and have been shown to be promising anti-viral targets. Here, Meyer et al. apply mass spectrometry to characterize the proteolytic cleavage profile of viral and cellular proteins in vitro.
Published: 2021
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234. 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
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235. Autoantibodies Neutralizing Type I Interferons in 20% of COVID-19 Deaths in a French Hospital

Author: Paul Bastard, Adrian Gervais, Emmanuelle Jouanguy, Antoine Servajean, Angelique Chauvineau-Grenier, Aurélie Cobat, Benjamin Rossi, Jean-Laurent Casanova, Jérémie Rosain, Hôpital Robert Ballanger [Aulnay-sous-Bois], Human genetics of infectious diseases : Mendelian predisposition (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), St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANR-20-COVI-0003), ANRS Nord-Sud (ANRS-COV05), ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir—Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), and the University of Paris. PB was supported by the French Foundation for Medical Research (FRM, EA20170638020). PB and JR were supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller)., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité, Equipe HAL, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé - - GENCOVID2020 - ANR-20-COVI-0003 - COVID-19 - VALID, Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères - - GENVIR2020 - ANR-20-CE93-0003 - AAPG2020 - VALID, Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19. - - AABIFNCOV2020 - ANR-20-CO11-0001 - COVID-19 - VALID, and European Advanced infraStructure for Innovative Genomics - EASI-Genomics - - H2020-INFRAIA-2018-12019-02-01 - 2023-07-31 - 824110 - VALID
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Article, Immunity, Internal medicine, medicine, Type I interferons, Immunology and Allergy, Humans, Autoantibodies, business.industry, SARS-CoV-2, Autoantibody, COVID-19, medicine.disease, mortality, Hospitals, Pneumonia, Increased risk, Cohort, Interferon Type I, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Article, business
Abstract: Recent studies reported the presence of pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) in at least 15% of patients with critical or severe COVID-19 pneumonia. In one study, these auto-Abs were found in almost 20% of deceased patients across all ages. We aimed to assess the prevalence and clinical impact of the auto-Abs to type I IFNs in Seine-Saint-Denis district, which was one of the most affected areas by COVID-19 in France during the first wave. We tested for the presence of auto-Abs neutralizing type I IFNs in a cohort of patients admitted for critical COVID-19 pneumonia during the first wave in the spring of 2020 in medicine departments at Robert Ballanger Hospital, Aulnay sous Bois. We found circulating auto-Abs that neutralized 100 pg/mL IFN-α2 and/or IFN-ω in plasma 1/10 in 7.9% (11 of 139) of patients hospitalized for critical COVID-19. The presence of neutralizing auto-Abs was associated with an increased risk of mortality as these auto-Abs were detected in 21% of patients who died from COVID-19 pneumonia. Deceased patients with and without auto-Abs did not present overt clinical differences. These results confirm both the importance of IFN-I immunity in host defense against SARS-CoV-2 infection and the usefulness of detection of auto-Abs neutralizing type I IFNs in the management of patients.
Published: 2021
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236. Genomic epidemiology and strain taxonomy of Corynebacterium diphtheriae

Author: Edgar Badell, Julie Toubiana, Melanie Hennart, Sylvain Brisse, Alexis Criscuolo, Julien Guglielmini, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Collège Doctoral, Sorbonne Université (SU), Centre national de Référence des Corynebactéries du Complexe Diphtheriae - National Reference Center Corynebacteria of the diphtheriae complex (CNR), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Biologie Computationnelle - Department of Computational Biology, This research was funded, in whole or in part, by Institut Pasteur and Santé publique France. For the purpose of open access, the authors have applied a CC-BY public copyright license to any Author Manuscript version arising from this submission, Received financial support from the French Government Investissement d’Avenir Programme Laboratoire d’Excellence on Integrative Biology of Emerging Infectious Diseases (ANR-10-LABX-62-IBEID). M.H. was supported financially by a PhD grant from the European Joint Programme One Health, which has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 570773830, We thank Melody Dazasfor assistance in the early steps of the project and Annick Carmi-Leroy, Annie Landier, Nathalie Armatys and Virginie Passet for technical assistance with the microbiological characterization and sequencing of the Corynebacterium diphtheriaestrains from the National Reference Center. We thank Vincent Enouf and the P2M core facility of Institut Pasteur for genomic sequencing. This work used the computational and storage services (TARS cluster) provided by the IT department at the Institut Pasteur, Paris, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health)(2018), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Collège doctoral [Sorbonne universités], and European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health EJP)(2018)
Subjects: OHEJP, Microbiology (medical), Epidemiology, [SDV]Life Sciences [q-bio], Genomics, Genome, 03 medical and health sciences, Humans, Genotyping, Phylogeny, 030304 developmental biology, Corynebacterium diphtheriae, Genetics, 0303 health sciences, Phylogenetic tree, biology, 030306 microbiology, Strain (biology), Microevolution, Diphtheria, Codes4strains, biology.organism_classification, 3. Good health, microevolution, Multilocus sequence typing, cgMLST, Genome, Bacterial, Multilocus Sequence Typing
Abstract: Corynebacterium diphtheriaeis highly transmissible and can cause large diphtheria outbreaks where vaccination coverage is insufficient. Sporadic cases or small clusters are observed in high-vaccination settings. The phylogeography and short timescale evolution ofC. diphtheriaeare not well understood, in part due to a lack of harmonized analytical approaches of genomic surveillance and strain tracking. We combined 1,305 genes with highly reproducible allele calls into a core genome multilocus sequence typing (cgMLST) scheme. We analyzed cgMLST gene diversity among 602 isolates from sporadic clinical cases, small clusters, or large outbreaks. We defined sublineages based on the phylogenetic structure withinC. diphtheriaeand strains based on the highest number of cgMLST mismatches within documented outbreaks. We performed time-scaled phylogenetic analyses of major sublineages. The cgMLST scheme showed high allele call rate inC. diphtheriaeand the closely related speciesC. belfantiiandC. rouxii. We demonstrate its utility to delineate epidemiological case clusters and outbreaks using a 25 mismatches threshold and reveal a number of cryptic transmission chains, most of which are geographically restricted to one or a few adjacent countries. Subcultures of the vaccine strain PW8 differed by up to 20 cgMLST mismatches. Phylogenetic analyses revealed a short-timescale evolutionary gain or loss of the diphtheria toxin and biovar-associated genes. We devised a genomic taxonomy of strains and deeper sublineages (defined using a 500-cgMLST-mismatch threshold), currently comprising 151 sublineages, only a few of which are geographically widespread based on current sampling. The cgMLST genotyping tool and nomenclature was made publicly accessible (https://bigsdb.pasteur.fr/diphtheria). Standardized genome-scale strain genotyping will help tracing transmission and geographic spread ofC. diphtheriae. The unified genomic taxonomy ofC. diphtheriaestrains provides a common language for studies of ecology, evolution, and virulence heterogeneity amongC. diphtheriaesublineages.
Published: 2021
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237. The CovR regulatory network drives the evolution of Group B Streptococcus virulence

Author: Maria-Vittoria, Mazzuoli, Maëlle, Daunesse, Hugo, Varet, Isabelle, Rosinski-Chupin, Rachel, Legendre, Odile, Sismeiro, Myriam, Gominet, Pierre Alexandre, Kaminski, Philippe, Glaser, Claudia, Chica, Patrick, Trieu-Cuot, Arnaud, Firon, Biologie des Bactéries pathogènes à Gram-positif - Biology of Gram-Positive Pathogens, 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), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-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] (IP)-Institut Pasteur [Paris] (IP), Écologie et Évolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), This work was supported by grants from the French Government ‘Laboratory of Excellence - Integrative Biology of Emerging Infectious Diseases’ (LabEx IBEID, grant number ANR-10-LABX-62-IBEID to PTC), the Fondation pour la Recherche Médicale (FRM grant number DEQ20181039599 to PTC), and the ANR (HemeDetox grant number ANR-17-CE11-0044-03 to AF)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-17-CE11-0044,HemeDetox,Understanding heme stress sensing system by pathogens, to design new antibiotics(2017), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED BioSPC), Université Sorbonne Paris Cité (USPC)-Université de Paris (UP), Institut Pasteur [Paris]-Institut Pasteur [Paris], Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), and Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Transcription, Genetic, Virulence Factors, Prophages, [SDV]Life Sciences [q-bio], Gene Expression, QH426-470, Pathology and Laboratory Medicine, Biochemistry, Microbiology, Streptococcus agalactiae, Bacterial Proteins, Gene Types, Microbial Physiology, Medicine and Health Sciences, Genetics, Humans, Gene Regulatory Networks, Gene Regulation, Bacterial Physiology, Post-Translational Modification, Phosphorylation, Promoter Regions, Genetic, Regulons, Virulence, Transcriptional Control, Biology and Life Sciences, Proteins, Bacteriology, Chromosomes, Bacterial, Adhesins, Genes, Bacterial, Genetic Loci, Host-Pathogen Interactions, Regulator Genes, Pathogens, Research Article
Abstract: Virulence of the neonatal pathogen Group B Streptococcus is under the control of the master regulator CovR. Inactivation of CovR is associated with large-scale transcriptome remodeling and impairs almost every step of the interaction between the pathogen and the host. However, transcriptome analyses suggested a plasticity of the CovR signaling pathway in clinical isolates leading to phenotypic heterogeneity in the bacterial population. In this study, we characterized the CovR regulatory network in a strain representative of the CC-17 hypervirulent lineage responsible of the majority of neonatal meningitis. Transcriptome and genome-wide binding analysis reveal the architecture of the CovR network characterized by the direct repression of a large array of virulence-associated genes and the extent of co-regulation at specific loci. Comparative functional analysis of the signaling network links strain-specificities to the regulation of the pan-genome, including the two specific hypervirulent adhesins and horizontally acquired genes, to mutations in CovR-regulated promoters, and to variability in CovR activation by phosphorylation. This regulatory adaptation occurs at the level of genes, promoters, and of CovR itself, and allows to globally reshape the expression of virulence genes. Overall, our results reveal the direct, coordinated, and strain-specific regulation of virulence genes by the master regulator CovR and suggest that the intra-species evolution of the signaling network is as important as the expression of specific virulence factors in the emergence of clone associated with specific diseases., Author summary Streptococcus agalactiae, commonly known as the Group B Streptococcus (GBS), is a commensal bacterium of the intestinal and vaginal tracts found in approximately 30% of healthy adults. However, GBS is also an opportunistic pathogen and the leading cause of neonatal invasive infections. Epidemiologic data have identified a particular GBS clone, designated the CC-17 hypervirulent clonal complex, as responsible for the overwhelming majority of neonatal meningitis. The hypervirulence of CC-17 has been linked to the expression of two specific surface proteins increasing their abilities to cross epithelial and endothelial barriers. In this study, we characterized the role of the major regulator of virulence gene expression, the CovR response regulator, in a representative hypervirulent strain. Transcriptome and genome-wide binding analysis reveal the architecture of the CovR signaling network characterized by the direct repression of a large array of virulence-associated genes, including the specific hypervirulent adhesins. Comparative analysis in a non-CC-17 wild type strain demonstrates a high level of plasticity of the regulatory network, allowing to globally reshape pathogen-host interaction. Overall, our results suggest that the intra-species evolution of the regulatory network is an important factor in the emergence of GBS clones associated with specific pathologies.
Published: 2021
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238. 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
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239. Microbiome-pathogen interactions drive epidemiological dynamics of antibiotic resistance: A modeling study applied to nosocomial pathogen control

Author: Smith, DR, Temime, L, Opatowski, L, Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris] (IP)-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), 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), The work was supported directly by internal resources from the French National Institute for Health and Medical Research, the Institut Pasteur, the Conservatoire National des Arts et Métiers, and the University of Versailles–Saint-Quentin-en-Yvelines / University of Paris-Saclay. This study received funding from the French Government’s ‘Investissement d’Avenir’ program, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (Grant ANR-10-LABX-62- IBEID). DS is supported by a Canadian Institutes of Health Research Doctoral Foreign Study Award (Funding Reference Number 164263) and all authors are supported by the French government through its National Research Agency project SPHINX-17-CE36-0008-01., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-17-CE36-0008,SPHINx,Diffusion de pathogènes au sein des réseaux de soins : une étude de modélisation(2017), Bertram, Marie-Liesse, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Diffusion de pathogènes au sein des réseaux de soins : une étude de modélisation - - SPHINx2017 - ANR-17-CE36-0008 - AAPG2017 - VALID
Subjects: MESH: Drug Resistance, Microbial, QH301-705.5, Science, global health, antibiotics, K. pneumoniae, MESH: Anti-Bacterial Agents, microbiota, Humans, MESH: Microbiota, human, Biology (General), MESH: Models, Theoretical, Cross Infection, MESH: Humans, Bacteria, E. coli, MESH: Cross Infection, Drug Resistance, Microbial, Models, Theoretical, S. aureus, within-host interactions, Anti-Bacterial Agents, MESH: Bacteria, Epidemiology and Global Health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Medicine, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Other, C. difficile, ecology, Research Article
Abstract: International audience; The human microbiome can protect against colonization with pathogenic antibiotic-resistant bacteria (ARB), but its impacts on the spread of antibiotic resistance are poorly understood. We propose a mathematical modeling framework for ARB epidemiology formalizing within-host ARB-microbiome competition, and impacts of antibiotic consumption on microbiome function. Applied to the healthcare setting, we demonstrate a trade-off whereby antibiotics simultaneously clear bacterial pathogens and increase host susceptibility to their colonization, and compare this framework with a traditional strain-based approach. At the population level, microbiome interactions drive ARB incidence, but not resistance rates, reflecting distinct epidemiological relevance of different forces of competition. Simulating a range of public health interventions (contact precautions, antibiotic stewardship, microbiome recovery therapy) and pathogens ( Clostridioides difficile , methicillin-resistant Staphylococcus aureus , multidrug-resistant Enterobacteriaceae) highlights how species-specific within-host ecological interactions drive intervention efficacy. We find limited impact of contact precautions for Enterobacteriaceae prevention, and a promising role for microbiome-targeted interventions to limit ARB spread.
Published: 2021
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240. High-throughput identification of viral termini and packaging mechanisms in virome datasets using PhageTermVirome

Author: Garneau, Julian, Legrand, Véronique, Marbouty, Martial, Press, Maximilian, Vik, Dean, Fortier, Louis-Charles, Sullivan, Matthew, Bikard, David, Monot, Marc, Biomics (plateforme technologique), Institut Pasteur [Paris], Infrastructure et Ingénierie scientifique (plateforme), Régulation spatiale des Génomes - Spatial Regulation of Genomes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Phase Genomics [Seattle], Ohio State University [Columbus] (OSU), Université de Sherbrooke (UdeS), Biologie de Synthèse - Synthetic biology, This work was supported by the French Government’s program Investissement d’Avenir program, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ [ANR-10-LABX-62-IBEID] and the Natural Sciences and Engineering Research Council of Canada (NSERC #341450-2010). Biomics Platform, C2RT, Institut Pasteur, Paris, France, is supported by France Génomique (ANR-10-INBS-09-09) and the Infrastructures de recherche en biologie, santé et agronomie (IBISA)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), and 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)
Subjects: Science, [SDV]Life Sciences [q-bio], viruses, Phage biology, Genome, Viral, Genome informatics, Microbiology, Article, Workflow, Virology, Databases, Genetic, Sequencing, Bacteriophages, Virome, High-throughput screening, Computational Biology, High-Throughput Nucleotide Sequencing, Genomics, Viral Packaging Sequence, Computational biology and bioinformatics, Data processing, Medicine, Metagenomics, Algorithms, Software
Abstract: International audience; Viruses that infect bacteria (phages) are increasingly recognized for their importance in diverse ecosystems but identifying and annotating them in large-scale sequence datasets is still challenging. Although efficient scalable virus identification tools are emerging, defining the exact ends (termini) of phage genomes is still particularly difficult. The proper identification of termini is crucial, as it helps in characterizing the packaging mechanism of bacteriophages and provides information on various aspects of phage biology. Here, we introduce PhageTermVirome (PTV) as a tool for the easy and rapid high-throughput determination of phage termini and packaging mechanisms using modern large-scale metagenomics datasets. We successfully tested the PTV algorithm on a mock virome dataset and then used it on two real virome datasets to achieve the rapid identification of more than 100 phage termini and packaging mechanisms, with just a few hours of computing time. Because PTV allows the identification of free fully formed viral particles (by recognition of termini present only in encapsidated DNA), it can also complement other virus identification softwares to predict the true viral origin of contigs in viral metagenomics datasets. PTV is a novel and unique tool for high-throughput characterization of phage genomes, including phage termini identification and characterization of genome packaging mechanisms. This software should help researchers better visualize, map and study the virosphere. PTV is freely available for downloading and installation at https://gitlab.pasteur.fr/vlegrand/ptv .
Published: 2021
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241. Comparative genomic analysis of Methanimicrococcus blatticola provides insights into host adaptation in archaea and the evolution of methanogenesis

Author: Thomas, Courtney, Taib, Najwa, Gribaldo, Simonetta, Borrel, Guillaume, 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), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), CMT is supported by a PhD fellowship from Paris Sorbonne Université Science and by funds from the doctoral school Bio Sorbonne Paris Cité 'BioSPC'. GB acknowledges funding from the French National Agency for Research Grant Methevol (ANR-19-CE02-0005-01) and SG acknowledges Archaevol (ANR-16-CE02-0005-01). This study has received funding from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant no. ANR-10-LABX-62-IBEID)., ANR-19-CE02-0005,METHEVOL,Caractérisation de nouveaux acteurs et des transitions évolutives dans le métabolisme du méthane, un métabolisme clef dans l'évolution du domaine Archaea(2019), ANR-16-CE02-0005,Arch-Evol,Approches phylogenomiques pour étudier l'origine et évolution des Archées(2016), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Abstract: International audience; Abstract Other than the Methanobacteriales and Methanomassiliicoccales, the characteristics of archaea that inhabit the animal microbiome are largely unknown. Methanimicrococcus blatticola , a member of the Methanosarcinales, currently reunites two unique features within this order: it is a colonizer of the animal digestive tract and can only reduce methyl compounds with H 2 for methanogenesis, a increasingly recognized metabolism in the archaea and whose origin remains debated. To understand the origin of these characteristics, we have carried out a large-scale comparative genomic analysis. We infer the loss of more than a thousand genes in M. blatticola , by far the largest genome reduction across all Methanosarcinales. These include numerous elements for sensing the environment and adapting to more stable gut conditions, as well as a significant remodeling of the cell surface components likely involved in host and gut microbiota interactions. Several of these modifications parallel those previously observed in phylogenetically distant archaea and bacteria from the animal microbiome, suggesting large-scale convergent mechanisms of adaptation to the gut. Strikingly, M. blatticola has lost almost all genes coding for the H 4 MPT methyl branch of the Wood–Ljungdahl pathway (to the exception of mer ), a phenomenon never reported before in any member of Class I or Class II methanogens. The loss of this pathway illustrates one of the evolutionary processes that may have led to the emergence of methyl-reducing hydrogenotrophic methanogens, possibly linked to the colonization of organic-rich environments (including the animal gut) where both methyl compounds and hydrogen are abundant.
Published: 2021
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242. sgDI-tector: defective interfering viral genome bioinformatics for detection of coronavirus subgenomic RNAs

Author: Andrea Di Gioacchino, Rachel Legendre, Yannis Rahou, Valérie Najburg, Pierre Charneau, Benjamin D. Greenbaum, Frédéric Tangy, Sylvie van der Werf, Simona Cocco, Anastassia V. Komarova, Physique pour la médecine (PhysMed Paris), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (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), Physique Statistique et Inférence pour la Biologie, Laboratoire de physique de l'ENS - ENS Paris (LPENS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, 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), Laboratoire d’innovation : vaccins – Innovation lab : vaccines, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris] (IP)-TheraVectys-Université Paris Cité (UPCité), Memorial Sloane Kettering Cancer Center [New York], Weill Cornell Medicine [Cornell University], Cornell University [New York], We acknowledge the ANR (Agence Nationale de la Recherche) and FRM (Fondation de la Recherche Médicale) for funding this work through the AAP Flash-Covid 19 project SARS-Cov-2immunRNAs. A.V.K. received support from ANR through the grant ANR-LBX-62 IBEID CoV-2SENSING/COVID 19. RNA NGS has been supported by France Génomique (ANR-10-INBS-09-09)., We would like to thank J. Pipoli da Fonseca, L. Lemée from Biomics Platform, C2RT, Institut Pasteur, Paris, France for RNA NGS, IBISA and the Illumina COVID-19 Projects’ offer. The authors would like to thank members of the Tangy, van der Werf laboratories and the National Reference Center (CNR) for Respiratory Viruses at the Institut Pasteur for support and valuable discussions., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Weill Cornell Medicine [New York], Legendre, Rachel, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID
Subjects: viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Computational biology, Genome, Viral, Biology, ENCODE, medicine.disease_cause, Genome, Open Reading Frames, medicine, MESH: SARS-CoV-2, Viral rna, user-friendly bioinformatics, MESH: High-Throughput Nucleotide Sequencing, Molecular Biology, Polymerase, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Subgenomic mRNA, Coronavirus, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, subgenomic RNA, SARS-CoV-2, RNA, Computational Biology, High-Throughput Nucleotide Sequencing, MESH: Open Reading Frames, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: RNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, defective viral genomes, biology.protein, RNA, Viral, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Genome, Viral, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Computational Biology
Abstract: Coronavirus RNA-dependent RNA polymerases produce subgenomic RNAs (sgRNAs) that encode viral structural and accessory proteins. User-friendly bioinformatic tools to detect and quantify sgRNA production are urgently needed to study the growing number of next-generation sequencing (NGS) data of SARS-CoV-2. We introduced sgDI-tector to identify and quantify sgRNA in SARS-CoV-2 NGS data. sgDI-tector allowed detection of sgRNA without initial knowledge of the transcription-regulatory sequences. We produced NGS data and successfully detected the nested set of sgRNAs with the ranking M>ORF3a>N>ORF6>ORF7a>ORF8>S>E>ORF7b. We also compared the level of sgRNA production with other types of viral RNA products such as defective interfering viral genomes.
Published: 2021
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243. Assessing the feasibility of Nipah vaccine efficacy trials based on previous outbreaks in Bangladesh

Author: Marc Lipsitch, Stephen P. Luby, Gabriel Ribeiro Dos Santos, Henrik Salje, Mahmudur Rahman, Emily S. Gurley, Birgit Nikolay, 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), University of Cambridge [UK] (CAM), Harvard T.H. Chan School of Public Health, Stanford University, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), B. N. and S. C. acknowledge the support of the Laboratory of Excellence Integrative Biology of Emerging Infectious Diseases (Grant ANR-10-LABX-62-IBEID), the National Institute of General Medical Sciences Models of Infectious Disease Agent Study Initiative, the AXA Research Fund and the INCEPTION project (PIA/ANR-16-CONV-0005). B. N., E. G. and H. S. acknowledge the support of the Defense Advanced Research Projects Agency (Grant D18AC00031)., 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), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, 030231 tropical medicine, Context (language use), Nipah virus, Disease cluster, Disease Outbreaks, 03 medical and health sciences, 0302 clinical medicine, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Epidemiology, medicine, Animals, Humans, 030212 general & internal medicine, 030304 developmental biology, 0303 health sciences, Bangladesh, Vaccines, General Veterinary, General Immunology and Microbiology, business.industry, vaccine trial, Clinical study design, Public Health, Environmental and Occupational Health, Vaccine trial, Vaccine efficacy, 3. Good health, Vaccination, Infectious Diseases, Case-Control Studies, Emergency medicine, Molecular Medicine, Feasibility Studies, Observational study, Emerging pathogens, business
Abstract: BackgroundNipah virus (NiV) is an emerging, bat-borne pathogen that can be transmitted from person-to-person. Vaccines are currently being developed for NiV, and studies funded to evaluate their safety and immunogenicity, so that they could possibly be used to contain outbreaks. An important unanswered question is whether it will be possible to evaluate the efficacy of vaccine candidates in phase III clinical trials in a context where spillovers from the zoonotic reservoir are infrequent and associated with small outbreaks. The objective of this study was to investigate the feasibility of conducting a phase III vaccine trial in Bangladesh, the only country reporting regularly NiV cases.MethodsWe used simulations based on previously observed NiV cases from Bangladesh, an assumed vaccine efficacy of 90% and other NiV vaccine target characteristics, to compare three vaccination study designs: (i) cluster randomized ring vaccination, (ii) cluster randomized mass vaccination, and (iii) an observational case-control study design.ResultsThe simulations showed that, assuming a ramp-up period of 10 days and a mean hospitalization delay of 4 days, it would take 516 years and over 163,000 vaccine doses to run a ring vaccination trial under current epidemic conditions. A cluster-randomized trial in the two most affected districts would take 81 years and 2.3 million vaccine doses. An observational case-control design in these two districts would require seven years and 2.5 million vaccine doses.DiscussionWithout a change in the epidemiology of NiV, ring vaccination or cluster-randomized trials are unlikely to be completed within a reasonable time window. In this light, the remaining options are: (i) not conducting a phase III trial until the epidemiology of NiV changes, (ii) identifying alternative ways to licensure such as observational studies or controlled studies in animals such as in the US Food and Drug Administration’s (FDA) Animal Rule.
Published: 2021
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244. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19

Author: Asano, Takaki, Boisson, Bertrand, Onodi, Fanny, Matuozzo, Daniela, Moncada-Velez, Marcela, Maglorius Renkilaraj, Majistor Raj Luxman, Zhang, Peng, Meertens, Laurent, Bolze, Alexandre, Materna, Marie, Korniotis, Sarantis, Gervais, Adrian, Talouarn, Estelle, Bigio, Benedetta, Seeleuthner, Yoann, Bilguvar, Kaya, Zhang, Yu, Neehus, Anna-Lena, Ogishi, Masato, Pelham, Simon J., Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Soler-Palacín, Pere, Colobran, Roger, Martin-Nalda, Andrea, Rivière, Jacques G., Tandjaoui-Lambiotte, Yacine, Chaïbi, Khalil, Shahrooei, Mohammad, Darazam, Ilad Alavi, Olyaei, Nasrin Alipour, Mansouri, Davood, Hatipoğlu, Nevin, Palabiyik, Figen, Ozcelik, Tayfun, Novelli, Giuseppe, Novelli, Antonio, Casari, Giorgio, Aiuti, Alessandro, Carrera, Paola, Bondesan, Simone, Barzaghi, Federica, Rovere-Querini, Patrizia, Tresoldi, Cristina, Franco, Jose Luis, Rojas, Julian, Reyes, Luis Felipe, Bustos, Ingrid G., Arias, Andres Augusto, Morelle, Guillaume, Kyheng, Christèle, Troya, Jesús, Planas-Serra, Laura, Schlüter, Agatha, Gut, Marta, Pujol, Aurora, Allende, Luis M., Rodriguez-Gallego, Carlos, Flores, Carlos, Cabrera-Marante, Oscar, Pleguezuelo, Daniel E., Pérez de Diego, Rebeca, Keles, Sevgi, Aytekin, Gokhan, Metin Akcan, Ozge, Bryceson, Yenan T., Bergman, Peter, Brodin, Petter, Smole, Daniel, Smith, C. I. Edvard, Norlin, Anna-Carin, Campbell, Tessa M., Covill, Laura E., Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Mane, Shrikant, Marr, Nico, Ata, Manar, Al Ali, Fatima, Khan, Taushif, Spaan, András N., Dalgard, Clifton L., Bonfanti, Paolo, Biondi, Andrea, Tubiana, Sarah, Burdet, Charles, Nussbaum, Robert, Kahn-Kirby, Amanda, Snow, Andrew L., Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Zhang, Shen-Ying, Béziat, Vivien, Lifton, Richard P., Bastard, Paul, Notarangelo, Luigi D., Abel, Laurent, Su, Helen C., Jouanguy, Emmanuelle, Amara, Ali, Soumelis, Vassili, Cobat, Aurélie, Zhang, Qian, Casanova, Jean-Laurent, Al-Muhsen, Saleh, Al-Mulla, Fahd, Anderson, Mark S., Andreakos, Evangelos, Arias, Andrés A., Feldman, Hagit Baris, Belot, Alexandre, Biggs, Catherine M., Bogunovic, Dusan, Bondarenko, Anastasiia, Bousfiha, Ahmed A., Bryceson, Yenan, Bustamante, Carlos D., Butte, Manish J., Chakravorty, Samya, Christodoulou, John, Condino-Neto, Antonio, Constantinescu, Stefan N., Cooper, Megan A., Desai, Murkesh, Drolet, Beth A., El Baghdadi, Jamila, Espinosa-Padilla, Sara, Fellay, Jacques, Franco, José Luis, Froidure, Antoine, Gregersen, Peter K., Haerynck, Filomeen, Hagin, David, Halwani, Rabih, Heath, James R., Henrickson, Sarah E., Hsieh, Elena W.Y., Husebye, Eystein, Imai, Kohsuke, Itan, Yuval, Jarvis, Erich D., Karamitros, Timokratis, Kisand, Kai, Ku, Cheng-Lung, Lau, Yu-Lung, Ling, Yun, Lucas, Carrie L., Maniatis, Tom, Maródi, László, Meyts, Isabelle, Milner, Joshua D., Mironska, Kristina, Mogensen, Trine H., Morio, Tomohiro, Ng, Lisa F.P., O'Farrelly, Cliona, Okada, Satoshi, de Diego, Rebeca Perez, Planas, Anna M., Prando, Carolina, Quintana-Murci, Lluis, Renia, Laurent, Resnick, Igor, Rodríguez-Gallego, Carlos, Sancho-Shimizu, Vanessa, Sediva, Anna, Seppänen, Mikko R.J., Shahrooei, Mohammed, Shcherbina, Anna, Slaby, Ondrej, Tancevski, Ivan, Tangye, Stuart G., Abou Tayoun, Ahmad, Ramaswamy, Sathishkumar, Turvey, Stuart E, Uddin, K M Furkan, Uddin, Mohammed J., van de Beek, Diederik, Vinh, Donald C., von Bernuth, Horst, Zatz, Mayana, Zawadzki, Pawel, Foti, Giuseppe, Bellani, Giacomo, Citerio, Giuseppe, Contro, Ernesto, Pesci, Alberto, Valsecchi, Maria Grazia, Cazzaniga, Marina, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Roblero Albisures, Jonathan Antonio, Aldave, Juan C, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, AlKhater, Suzan A., Allardet-Servent, Jerome, Allende, Luis M, Alonso-Arias, Rebeca, Alshahrani, Mohammed S, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Arrestier, Romain, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Barrou, Benoit, Barzagh, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousfiha, Ahmed A, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Boyarchuk, Oksana, Bravais, Juliette, Briones, M. Luisa, Brunner, Marie-Eve, Bruno, Raffaele, Bueno, Maria Rita P, Bukhari, Huda, Cáceres Agra, Juan José, Capra, Ruggero, Carapito, Raphael, Carrabba, Maria, Casasnovas, Carlos, Caseris, Marion, Cassaniti, Irene, Castelle, Martin, Castelli, Francesco, de Vera, Martín Castillo, Castro, Mateus V, Catherinot, Emilie, Celik, Jale Bengi, Ceschi, Alessandro, Chalumeau, Martin, Charbit, Bruno, Cheng, Matthew P., Clavé, Père, Clotet, Bonaventura, Codina, Anna, Cohen, Yves, Comarmond, Cloé, Combes, Alain, Comoli, Patrizia, Corsico, Angelo G, Coşkuner, Taner, Cvetkovski, Aleksandar, Cyrus, Cyril, Dalmau, David, Danion, François, Darley, David Ross, Das, Vincent, Dauby, Nicolas, Dauger, Stéphane, De Munter, Paul, de Pontual, Loic, Dehban, Amin, Delplancq, Geoffroy, Demoule, Alexandre, Desguerre, Isabelle, Di Sabatino, Antonio, Diehl, Jean-Luc, Dobbelaere, Stephanie, Domínguez-Garrido, Elena, Dubost, Clément, Ekwall, Olov, Bozdemir, Şefika Elmas, Elnagdy, Marwa H, Emiroglu, Melike, Endo, Akifumi, Erdeniz, Emine Hafize, Aytekin, Selma Erol, Lasa, Maria Pilar Etxart, Euvrard, Romain, Fabio, Giovanna, Faivre, Laurence, Falck, Antonin, Fartoukh, Muriel, Faure, Morgane, Arquero, Miguel Fernandez, Ferrer, Ricard, Ferreres, Jose, Francois, Bruno, Fumadó, Victoria, Fung, Kitty S C, Fusco, Francesca, Gagro, Alenka, Solis, Blanca Garcia, Gaussem, Pascale, Gayretli, Zeynep, Gil-Herrera, Juana, Gilardin, Laurent, Gatineau, Audrey Giraud, Girona-Alarcón, Mònica, Cifuentes Godínez, Karen Alejandra, Goffard, Jean-Christophe, Gonzales, Nacho, Gonzalez-Granado, Luis I, González-Montelongo, Rafaela, Guerder, Antoine, Gülhan, Belgin, Gumucio, Victor Daniel, Hanitsch, Leif Gunnar, Gunst, Jan, Hadjadj, Jérôme, Hancerli, Selda, Hariyan, Tetyana, Hatipoglu, Nevin, Heppekcan, Deniz, Hernandez-Brito, Elisa, Ho, Po-ki, Holanda-Peña, María Soledad, Horcajada, Juan P, Hraiech, Sami, Humbert, Linda, Hung, Ivan F N, Iglesias, Alejandro D., Íñigo-Campos, Antonio, Jamme, Matthieu, Arranz, María Jesús, Jimeno, Marie-Thérèse, Jordan, Iolanda, Yüksek, Saliha Kanık, Kara, Yalcin Burak, Karahan, Aydın, Karbuz, Adem, Yasar, Kadriye Kart, Kasapcopur, Ozgur, Kashimada, Kenichi, Demirkol, Yasemin Kendir, Kido, Yasutoshi, Kizil, Can, Kılıç, Ahmet Osman, Klocperk, Adam, Koutsoukou, Antonia, Król, Zbigniew J., Ksouri, Hatem, Kuentz, Paul, Kwan, Arthur M C, Kwan, Yat Wah M, Kwok, Janette S Y, Lagier, Jean-Christophe, Lam, David S Y, Lampropoulou, Vicky, Lanternier, Fanny, LAU, Yu-Lung, Le Bourgeois, Fleur, Leo, Yee-Sin, Lopez, Rafael Leon, Leung, Daniel, Levin, Michael, Levy, Michael, Lévy, Romain, Li, Zhi, Lilleri, Daniele, Bolanos Lima, Edson Jose Adrian, Linglart, Agnes, López-Collazo, Eduardo, Lorenzo-Salazar, José M., Louapre, Céline, Lubetzki, Catherine, Lung, Kwok-Cheung, Luyt, Charles-Edouard, Lye, David C, Magnone, Cinthia, Marchioni, Enrico, Marioli, Carola, Marjani, Majid, Marques, Laura, Pereira, Jesus Marquez, Martín-Nalda, Andrea, Pueyo, David Martínez, Martinez-Picado, Javier, Marzana, Iciar, Mata-Martínez, Carmen, Mathian, Alexis, Matos, Larissa RB, Matthews, Gail V, Mayaux, Julien, McLaughlin-Garcia, Raquel, Meersseman, Philippe, Mège, Jean-Louis, Mekontso-Dessap, Armand, Melki, Isabelle, Meloni, Federica, Meritet, Jean-François, Merlani, Paolo, Akcan, Özge Metin, Mezidi, Mehdi, Migeotte, Isabelle, Millereux, Maude, Million, Matthieu, Mirault, Tristan, Mircher, Clotilde, Mirsaeidi, Mehdi, Mizoguchi, Yoko, Modi, Bhavi P, Mojoli, Francesco, Moncomble, Elsa, Melián, Abián Montesdeoca, Martinez, Antonio Morales, Morandeira, Francisco, Morange, Pierre-Emmanuel, Mordacq, Cléemence, Mouly, Stéphane J, Muñoz-Barrera, Adrián, Nafati, Cyril, Nagashima, Shintaro, Nakagama, Yu, Neven, Bénédicte, Neves, João Farela, Ng, Lisa FP, Ng, Yuk-Yung, Nielly, Hubert, Medina, Yeray Novoa, Cuadros, Esmeralda Nuñez, Ocejo-Vinyals, J. Gonzalo, Okamoto, Keisuke, Oualha, Mehdi, Ouedrani, Amani, Özçelik, Tayfun, Ozkaya-Parlakay, Aslinur, Pagani, Michele, Papadaki, Maria, Parizot, Christophe, Parola, Philippe, Pascreau, Tiffany, Paul, Stéphane, Paz-Artal, Estela, Pedraza, Sigifredo, González Pellecer, Nancy Carolina, Pellegrini, Silvia, de Diego, Rebeca Pérez, Pérez-Fernández, Xosé Luis, Philippe, Aurélien, Picod, Adrien, de Chambrun, Marc Pineton, Piralla, Antonio, Ploin, Dominique, Poissy, Julien, Poncelet, Géraldine, Poulakou, Garyphallia, Pouletty, Marie S, Pourshahnazari, Persia, Qiu-Chen, Jia Li, Quentric, Paul, Rambaud, Thomas, Raoult, Didier, Raoult, Violette, Rebillat, Anne-Sophie, Redin, Claire, Resmini, Léa, Ricart, Pilar, Richard, Jean-Christophe, Rigo-Bonnin, Raúl, Rivet, Nadia, Rivière, Jacques G, Rocamora-Blanch, Gemma, Rodero, Mathieu P, Rodrigo, Carlos, Rodriguez, Luis Antonio, Rodriguez-Palmero, Agustí, Romero, Carolina Soledad, Rothenbuhler, Anya, Roux, Damien, Rovina, Nikoletta, Rozenberg, Flore, Ruch, Yvon, Ruiz, Montse, Ruiz del Prado, Maria Yolanda, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril E, Scolari, Francesco, Seijo, Luis, Seminario, Analia Gisela, Sene, Damien, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Siguret, Virginie, Siouti, Eleni, Smadja, David M, Smith, Nikaia, Sobh, Ali, Solanich, Xavier, Solé-Violán, Jordi, Soler, Catherine, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon J, Tello, Loreto Vidaur, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, Thorn, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Triantafyllia, Vasiliki, Trouillet-Assant, Sophie, Tsang, Owen T Y, Tserel, Liina, Tso, Eugene Y K, Tucci, Alessandra, Tüter Öz, Şadiye Kübra, Ursini, Matilde Valeria, Utsumi, Takanori, Uzunhan, Yurdagul, Vabres, Pierre, Valencia-Ramos, Juan, Van Den Rym, Ana Maria, Vandernoot, Isabelle, Velez-Santamaria, Valentina, Zuniga Veliz, Silvia Patricia, Vidigal, Mateus C, Viel, Sébastien, Vilain, Cédric, Vilaire-Meunier, Marie E, Villar-García, Judit, Vincent, Audrey, Vogt, Guillaume, Voiriot, Guillaume, Volokha, Alla, Vuotto, Fanny, Wauters, Els, Wauters, Joost, Wu, Alan K L, Wu, Tak-Chiu, Yahşi, Aysun, Yesilbas, Osman, Yildiz, Mehmet, Young, Barnaby E, Yükselmiş, Ufuk, Zecca, Marco, Zuccaro, Valentina, Jens, Van Praet, Lambrecht, Bart N., Eva, Van Braeckel, Cédric, Bosteels, Levi, Hoste, Eric, Hoste, Bauters, Fré, De Clercq, Jozefien, Cathérine, Heijmans, Hans, Slabbynck, Leslie, Naesens, Florkin, Benoit, Boulanger, Cécile, Vanderlinden, Dimitri, Annereau, Jean-Philippe, Briseño-Roa, Luis, Gribouval, Olivier, Pelet, Anna, Andrejak, Claire, Angoulvant, 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Quentin, Le Mestre, Soizic, Le Nagard, Hervé, Lescure, François-Xavier, Letrou, Sophie, Levy, Yves, Lina, Bruno, Lingas, Guillaume, Lucet, Jean Christophe, Malvy, Denis, Mambert, Marina, Mentré, France, Meziane, Amina, Mouquet, Hugo, Mullaert, Jimmy, Neant, Nadège, Nguyen, Duc, Noret, Marion, Nseir, Saad, Papadopoulos, Aurélie, Paul, Christelle, Peiffer-Smadja, Nathan, Perpoint, Thomas, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pham, Huong, Picone, Olivier, Piquard, Valentine, Puéchal, Oriane, Rabaud, Christian, Rosa-Calatrava, Manuel, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Tellier, Marie-Capucine, Téoulé, François, Terrier, Olivier, Timsit, Jean-François, Tual, Christelle, Van Der Werf, Sylvie, Vanel, Noémie, Veislinger, Aurélie, Visseaux, Benoit, Wiedemann, Aurélie, Yazdanpanah, Yazdan, Alavoine, Loubna, Behillil, Sylvie, Charpentier, Charlotte, Dechanet, Aline, Ecobichon, Jean-Luc, Frezouls, Wahiba, Houhou, Nadhira, Lehacaut, Jonathan, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Quintin, Caroline, Thy, Michael, van der Werf, Sylvie, Vignali, Valérie, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Laine, Fabrice, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Lefévre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Kouakam, Christelle, Leturque, Nicolas, Roufai, Layidé, Amat, Karine, Espérou, Hélène, Hendou, Samia, van Agtmael, Michiel, Algera, Anne Geke, Appelman, Brent, van Baarle, Frank, Bax, Diane, Beudel, Martijn, Bogaard, Harm 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Marry, Stijnis, Cornelis S., Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa M, Tuinman, Pieter R., van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke A., van Vugt, Michèle, Wouters, Dorien, Zwinderman, A. H (Koos), Brouwer, Matthijs C., Wiersinga, W. Joost, Vlaar, Alexander P.J., Tompkins, Miranda F., Alba, Camille, Hupalo, Daniel N., Rosenberger, John, Sukumar, Gauthaman, Wilkerson, Matthew D., Zhang, Xijun, Lack, Justin, Oler, Andrew J., Dobbs, Kerry, Delmonte, Ottavia M., Danielson, Jeffrey J., Bettini, Laura Rachele, D’Angio, Mariella, Beretta, Ilaria, Imberti, Luisa, Sottini, Alessandra, Quaresima, Virginia, Quiros-Roldan, Eugenia, Rossi, Camillo, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Neurology, Infectious diseases, Center of Experimental and Molecular Medicine, APH - Aging & Later Life, APH - Global Health, APH - Quality of Care, AII - Amsterdam institute for Infection and Immunity, APH - Health Behaviors & Chronic Diseases, Global Health, APH - Methodology, Graduate School, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, APH - Digital Health, APH - Personalized Medicine, ACS - Microcirculation, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratory of Human Genetics of Infectious Diseases (Necker Branch - INSERM U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rockefeller University [New York], Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Helix [San Mateo, CA], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Özçelik, Tayfun, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Pathology, Asano, T., Boisson, B., Onodi, F., Matuozzo, D., Moncada-Velez, M., Renkilaraj, M. R. L. M., Zhang, P., Meertens, L., Bolze, A., Materna, M., Korniotis, S., Gervais, A., Talouarn, E., Bigio, B., Seeleuthner, Y., Bilguvar, K., Zhang, Y., Neehus, A. -L., Ogishi, M., Pelham, S. J., Le Voyer, T., Rosain, J., Philippot, Q., Soler-Palacin, P., Colobran, R., Martin-Nalda, A., Riviere, J. G., Tandjaoui-Lambiotte, Y., Chaibi, K., Shahrooei, M., Darazam, I. A., Olyaei, N. A., Mansouri, D., Hatipoglu, N., Palabiyik, F., Ozcelik, T., Novelli, G., Novelli, A., Casari, G., Aiuti, A., Carrera, P., Bondesan, S., Barzaghi, F., Rovere-Querini, P., Tresoldi, C., Franco, J. L., Rojas, J., Reyes, L. F., Bustos, I. G., Arias, A. A., Morelle, G., Kyheng, C., Troya, J., Planas-Serra, L., Schluter, A., Gut, M., Pujol, A., Allende, L. M., Rodriguez-Gallego, C., Flores, C., Cabrera-Marante, O., Pleguezuelo, D. E., Diego, R. P. D., Keles, S., Aytekin, G., Akcan, O. M., Bryceson, Y. T., Bergman, P., Brodin, P., Smole, D., Smith, C. I. E., Norlin, A. -C., Campbell, T. M., Covill, L. E., Hammarstrom, L., Pan-Hammarstrom, Q., Abolhassani, H., Mane, S., Marr, N., Ata, M., Ali, F. A., Khan, T., Spaan, A. N., Dalgard, C. L., Bonfanti, P., Biondi, A., Tubiana, S., Burdet, C., Nussbaum, R., Kahn-Kirby, A., Snow, A. L., Bustamante, J., Puel, A., Boisson-Dupuis, S., Zhang, S. -Y., Beziat, V., Lifton, R. P., Bastard, P., Notarangelo, L. D., Abel, L., Su, H. C., Jouanguy, E., Amara, A., Soumelis, V., Cobat, A., Zhang, Q., Casanova, J. -L., Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), 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)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, French COVID cohort study group, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, Rockefeller University, the St. Giles Foundation, the NIH (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at the George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01) and the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Fondation du Souffle, Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University of Paris. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 Research and Innovation Program (EasiGenomics grant no. 824110 COVID-19/PID12342). A.P., R.P.d.D., C.R.-G., and C.F. were funded by Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1, AEI/FEDER, UE), Fundación DISA (OA18/017), and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). The laboratories of G.N. and A.N. were supported by a grant awarded to Regione Lazio (PROGETTI DI GRUPPI DI RICERCA 2020) no. A0375-2020-36663, GecoBiomark. A. Amara’s laboratory was supported by ANR under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the FRM (EQU202003010193), ANR (ANR-20-COVI-000 project IDISCOVR and ANR-20-CO11-0004 project FISHBP), and the University of Paris (Plan de Soutien Covid-19: RACPL20FIR01-COVID-SOUL). This work was supported, in part, by the Division of Intramural Research, NIAID, NIH (grants 1ZIAAI001265 to H.C.S. and ZIA AI001270 to L.D.N.). The G.C. laboratory was supported by the Italian Ministry of Health (grant COVID-2020-12371617) and the intramural COVID Host Genetics program. The J.L.F. laboratory was supported, in part, by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX, 806-2018) and Colciencias contract 713-2016 (no. 111574455633). The V.S. laboratory was supported by ANR DENDRISEPSIS (ANR-17-CE15-0003) and ANR APCOD (ANR-17-CE15-0003-01), a Fast Grant from the Mercatus Center, FRM, University of Paris PLAN D’URGENCE COVID19. The N.M. laboratory was supported by Sidra Medicine (SDR400048) and the Qatar National Research Fund (grant No. NPRP9-251-3-045). A.-L.N. was supported by the Bettencourt Schueller Foundation and the International PhD program of the Imagine Institute. P. Bergman and C.I.E.S received support from the Center for Medical Innovation (CIMED), the Swedish Medical Research Council and the Stockholm County Council (ALF-project). Part of this work was generated within the European Reference Network for rare primary immunodeficiency, autoinflammatory and autoimmune diseases (RITA)., Members of French COVID Cohort Study Group: Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Marie Bartoli5, Romain Basmaci6, Sylvie Behilill7, Marine Beluze8, Dehbia Benkerrou9, Krishna Bhavsar4, Lila Bouadma4, Sabelline Bouchez10, Maude Bouscambert11, Minerva Cervantes-Gonzalez4, Anissa Chair4, Catherine Chirouze12, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cadiergues14, Eric d’Ortenzio5, Marie-Pierre Debray4, Lauren Deconinck4, Dominique Deplanque15, Diane Descamps4, Mathilde Desvallée16, Alpha Diallo5, Alphonsine Diouf13, Céline Dorival9, François Dubos17, Xavier Duval4, Brigitte Elharrar18, Philippine Eloy4, Vincent Enouf7, Hélène Esperou14, Marina Esposito-Farese4, Manuel Etienne19, Eglantine Ferrand Devouge19, Nathalie Gault4, Alexandre Gaymard11, Jade Ghosn4, Tristan Gigante20, Morgane Gilg20, Jérémie Guedj21, Alexandre Hoctin13, Isabelle Hoffmann4, Ikram Houas14, Jean-Sébastien Hulot22, Salma Jaafoura14, Ouifiya Kafif4, Florentia Kaguelidou23, Sabrina Kali4, Antoine Khalil4, Coralie Khan16, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre5, Hervé Le Nagard24, François-Xavier Lescure4, Sophie Letrou4, Yves Levy25, Bruno Lina11, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy26, Marina Mambert13, France Mentré4, Amina Meziane9, Hugo Mouquet7, Jimmy Mullaert4, Nadège Neant24, Duc Nguyen26, Marion Noret27, Saad Nseir17, Aurélie Papadopoulos14, Christelle Paul5, Nathan Peiffer-Smadja4, Thomas Perpoint28, Ventzislava Petrov-Sanchez5, Gilles Peytavin4, Huong Pham4, Olivier Picone6, Valentine Piquard4, Oriane Puéchal29, Christian Rabaud30, Manuel Rosa-Calatrava11, Bénédicte Rossignol20, Patrick Rossignol30, Carine Roy4, Marion Schneider4, Richa Su4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé9, Olivier Terrier11, Jean-François Timsit4, Christelle Tual31, Sarah Tubiana4, Sylvie Van Der Werf7, Noémie Vanel32, Aurélie Veislinger31, Benoit Visseaux4, Aurélie Wiedemann25, Yazdan Yazdanpanah4, ANR-17-CE15-0003,DENDRISEPSIS,Analyse systémique des cellules présentatrices d'antigène dans le sepsis humain(2017), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), Asano, T, Boisson, B, Onodi, F, Matuozzo, D, Moncada-Velez, M, Maglorius Renkilaraj, M, Zhang, P, Meertens, L, Bolze, A, Materna, M, Korniotis, S, Gervais, A, Talouarn, E, Bigio, B, Seeleuthner, Y, Bilguvar, K, Zhang, Y, Neehus, A, Ogishi, M, Pelham, S, Le Voyer, T, Rosain, J, Philippot, Q, Soler-Palacín, P, Colobran, R, Martin-Nalda, A, Rivière, J, Tandjaoui-Lambiotte, Y, Chaïbi, K, Shahrooei, M, Darazam, I, Olyaei, N, Mansouri, D, Hatipoğlu, N, Palabiyik, F, Ozcelik, T, Novelli, G, Novelli, A, Casari, G, Aiuti, A, Carrera, P, Bondesan, S, Barzaghi, F, Rovere-Querini, P, Tresoldi, C, Franco, J, Rojas, J, Reyes, L, Bustos, I, Arias, A, Morelle, G, Christèle, K, Troya, J, Planas-Serra, L, Schlüter, A, Gut, M, Pujol, A, Allende, L, Rodriguez-Gallego, C, Flores, C, Cabrera-Marante, O, Pleguezuelo, D, de Diego, R, Keles, S, Aytekin, G, Akcan, O, Bryceson, Y, Bergman, P, Brodin, P, Smole, D, Smith, C, Norlin, A, Campbell, T, Covill, L, Hammarström, L, Pan-Hammarström, Q, Abolhassani, H, Mane, S, Marr, N, Ata, M, Al Ali, F, Khan, T, Spaan, A, Dalgard, C, Bonfanti, P, Biondi, A, Tubiana, S, Burdet, C, Nussbaum, R, Kahn-Kirby, A, Snow, A, Bustamante, J, Puel, A, Boisson-Dupuis, S, Zhang, S, Béziat, V, Lifton, R, Bastard, P, Notarangelo, L, Abel, L, Su, H, Jouanguy, E, Amara, A, Soumelis, V, Cobat, A, Zhang, Q, and Casanova, J
Subjects: Male, SUBSETS, [SDV]Life Sciences [q-bio], Penetrance, REDUNDANT, COVID-19 (Malaltia), 0302 clinical medicine, Resposta immunitària, 80 and over, Medicine and Health Sciences, Medicine, Young adult, Child, X-linked recessive inheritance, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, 0303 health sciences, education.field_of_study, PYOGENIC BACTERIAL-INFECTIONS, virus diseases, Genetic Diseases, X-Linked, HUMANS, General Medicine, Middle Aged, PROTECTIVE IMMUNITY, 3. Good health, Pedigree, Settore MED/03, Immune System Diseases, Genetic Diseases, Child, Preschool, Cohort, medicine.symptom, SINGLE-STRANDED RNA, Adult, Adolescent, Aged, Alleles, COVID-19, Humans, Infant, Toll-Like Receptor 7, Young Adult, Immunology, Population, Asymptomatic, Article, 03 medical and health sciences, HOST-DEFENSE, Immune response, Allele, Preschool, education, 030304 developmental biology, TOLL-LIKE RECEPTORS, business.industry, RECOGNITION, Proteins, X-Linked, medicine.disease, Pneumonia, 3121 General medicine, internal medicine and other clinical medicine, PLASMACYTOID DENDRITIC CELLS, business, Proteïnes, 030215 immunology
Abstract: Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract. Funding: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, Rockefeller University; the St. Giles Foundation; the NIH (R01AI088364), the National Center for Advancing Translational Sciences (NCATS); NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at the George Mason University; the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956); the Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01) and the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM) (EQU201903007798); the FRM and ANR GENCOVID project, the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) projects; the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 824110 (EASI-genomics). The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 Research and Innovation Program (EasiGenomics grant no. 824110 COVID-19/PID12342). A.P., R.P.d.D., C.R.-G., and C.F. were funded by Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, UE), Fundación DISA (OA18/017), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). The laboratories of G.N. and A.N. were supported by a grant awarded to Regione Lazio (PROGETTI DI GRUPPI DI RICERCA 2020) no. A0375-2020-36663, GecoBiomark. A. Amara’s laboratory was supported by ANR under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the FRM (EQU202003010193), ANR (ANR-20-COVI-000 project IDISCOVR and ANR-20-CO11-0004 project FISHBP), and the University of Paris (Plan de Soutien Covid-19: RACPL20FIR01-COVID-SOUL). This work was supported, in part, by the Division of Intramural Research, NIAID, NIH (grants 1ZIAAI001265 to H.C.S. and ZIA AI001270 to L.D.N.). The G.C. laboratory was supported by the Italian Ministry of Health (grant COVID-2020-12371617) and the intramural COVID Host Genetics program. The J.L.F. laboratory was supported, in part, by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX; 806-2018) and Colciencias contract 713-2016 (no. 111574455633). The V.S. laboratory was supported by ANR DENDRISEPSIS (ANR-17-CE15-0003) and ANR APCOD (ANR-17-CE15-0003-01), a Fast Grant from the Mercatus Center, FRM, University of Paris PLAN D’URGENCE COVID19. The N.M. laboratory was supported by Sidra Medicine (SDR400048) and the Qatar National Research Fund (grant No. NPRP9-251-3-045)
Published: 2021
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245. Factors shaping the abundance and diversity of the gut archaeome across the animal kingdom

Author: Courtney M. Thomas, Elie Desmond-Le Quéméner, Simonetta Gribaldo, Guillaume Borrel, 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), Laboratoire de Biotechnologie de l'Environnement [Narbonne] (LBE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), PhD fellowship from Paris Sorbonne Universite Science and by funds from the doctoral school Bio Sorbonne Paris Cite 'BioSPC', French Government's Investissement d'Avenir program, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant n degrees ANR-10-LABX-62-IBEID), ANR-19-CE02-0005,METHEVOL,Caractérisation de nouveaux acteurs et des transitions évolutives dans le métabolisme du méthane, un métabolisme clef dans l'évolution du domaine Archaea(2019), ANR-16-CE02-0005,Arch-Evol,Approches phylogenomiques pour étudier l'origine et évolution des Archées(2016), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: Dietary Fiber, Mammals, Methanobacteriaceae, Multidisciplinary, Bacteria, General Physics and Astronomy, General Chemistry, Euryarchaeota, Methanobrevibacter, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Archaea, General Biochemistry, Genetics and Molecular Biology, RNA, Ribosomal, 16S, Animals, Phylogeny
Abstract: Archaea are common constituents of the gut microbiome of humans, ruminants, and termites but little is known about their diversity and abundance in other animals. Here, we analyse sequencing and quantification data of archaeal and bacterial 16S rRNA genes from 250 species of animals covering a large taxonomic spectrum. We detect the presence of archaea in 175 animal species belonging to invertebrates, fish, amphibians, birds, reptiles and mammals. We identify five dominant gut lineages, corresponding to Methanobrevibacter, Methanosphaera, Methanocorpusculum, Methanimicrococcus and “Ca. Methanomethylophilaceae”. Some archaeal clades, notably within Methanobrevibacter, are associated to certain hosts, suggesting specific adaptations. The non-methanogenic lineage Nitrososphaeraceae (Thaumarchaeota) is frequently present in animal samples, although at low abundance, but may have also adapted to the gut environment. Host phylogeny, diet type, fibre content, and intestinal tract physiology are major drivers of the diversity and abundance of the archaeome in mammals. The overall abundance of archaea is more influenced by these factors than that of bacteria. Methanogens reducing methyl-compounds with H2 can represent an important fraction of the overall methanogens in many animals. Together with CO2-reducing methanogens, they are influenced by diet and composition of gut bacteria. Our results provide key elements toward our understanding of the ecology of archaea in the gut, an emerging and important field of investigation.
Published: 2021
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246. Interactions of the Insect-Specific Palm Creek Virus with Zika and Chikungunya Viruses in Aedes Mosquitoes

Author: Koh, Cassandra, Henrion-Lacritick, Annabelle, Frangeul, L., Saleh, Maria-Carla, Virus et Interférence ARN - Viruses and RNA Interference, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was funded by the DARPA PREEMPT program managed by Dr. Rohit Chitale and Dr. Kerri Dugan and administered through DARPA Cooperative Agreement HR001118S0017 (the content of the information does not necessarily reflect the position or the policy of the U.S. government, and no official endorsement should be inferred). This work also received funding from Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID) to M-C.S., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: QH301-705.5, viruses, insect-specific virus, fungi, virus diseases, mosquito, biochemical phenomena, metabolism, and nutrition, complex mixtures, arbovirus, Aedes, ISV–arbovirus interference, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Biology (General), [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: Palm Creek virus (PCV) is an insect-specific flavivirus that can interfere with the replication of mosquito-borne flaviviruses in Culex mosquitoes, thereby potentially reducing disease transmission. We examined whether PCV could interfere with arbovirus replication in Aedes (Ae.) aegypti and Ae. albopictus mosquitoes, major vectors for many prominent mosquito-borne viral diseases. We infected laboratory colonies of Ae. aegypti and Ae. albopictus with PCV to evaluate infection dynamics. PCV infection was found to persist to at least 21 days post-infection and could be detected in the midguts and ovaries. We then assayed for PCV–arbovirus interference by orally challenging PCV-infected mosquitoes with Zika and chikungunya viruses. For both arboviruses, PCV infection had no effect on infection and transmission rates, indicating limited potential as a method of intervention for Aedes-transmitted arboviruses. We also explored the hypothesis that PCV–arbovirus interference is mediated by the small interfering RNA pathway in silico. Our findings indicate that RNA interference is unlikely to underlie the mechanism of arbovirus inhibition and emphasise the need for empirical examination of individual pairs of insect-specific viruses and arboviruses to fully understand their impact on arbovirus transmission.
Published: 2021
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247. Selection for non-specific adhesion is a driver of FimH evolution increasing Escherichia coli biofilm capacity

Author: Mari Yoshida, Jean-Marc Ghigo, Christophe Beloin, Stanislas Thiriet-Rupert, Leonie Mayer, Génétique des Biofilms - Genetics of Biofilms, 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), This work was supported by an Institut Pasteur grant, by the French government's Investissement d'Avenir Program, Laboratoire d'Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID) and by the Fondation pour la Recherche Médicale (FRM grant no. DEQ20180339185). M.Y. was supported by Institut Pasteur Roux Cantarini fellowship. S.T.-R was supported by the French National Research Agency (ANR), project EvolTolAB (ANR-18-CE13-0010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-18-CE13-0010,EvoTolAB,Evolution et dynamique de dissémination de la tolérance aux antibiotiques dans les biofilms(2018)
Subjects: Experimental evolution, Operon, Chemistry, Fimbria, Mutant, Biofilm, General Medicine, Adhesion, medicine.disease_cause, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, biofilm, Cell biology, Bacterial adhesin, type 1 fimbriae, positive selection, Escherichia coli, medicine, experimental evolution
Abstract: Bacterial interactions with surfaces rely on the coordinated expression and interplay of surface exposed adhesion factors. However, how bacteria dynamically modulate their vast repertoire of adhesins to achieve surface colonization is not yet well-understood. We used experimental evolution and positive selection for improved adhesion to investigate how an initially poorly adherent Escherichia coli strain increased its adhesion capacities to abiotic surfaces. We showed that all identified evolved clones acquired mutations located almost exclusively in the lectin domain of fimH, the gene coding for the α-D-mannose-specific tip adhesin of type 1 fimbriae. While most of these fimH mutants showed reduced mannose- binding ability, they all displayed enhanced binding to abiotic surfaces, indicating a trade-off between FimH-mediated specific and non-specific adhesion properties. Several of the identified mutations were already reported in FimH lectin domain of pathogenic and environmental E. coli, suggesting that, beyond patho-adaptation, FimH microevolution favoring non-specific surface adhesion could constitute a selective advantage for natural E. coli isolates. Consistently, although E. coli deleted for the fim operon still evolves an increased adhesion capacity, mutants selected in the Δfim background are outcompeted by fimH mutants revealing clonal interference for adhesion. Our study therefore provides insights into the plasticity of E. coli adhesion potential and shows that evolution of type 1 fimbriae is a major driver of the adaptation of natural E. coli to colonization.
Published: 2021
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248. Ongoing diphtheria outbreak in Yemen: a cross-sectional and genomic epidemiology study

Author: Badell Edgar, Alharazi Abdulilah, Criscuolo Alexis, Almoayed Khaled Abdullah Ali, Lefrancq Noémie, Bouchez Valerie, Guglielmini Julien, Hennart Melanie, Carmi-Leroy Annick, Zidane Nora, Pascal-Perrigault Marine, Lebreton Manon, Martini Helena, Salje Henrik, Toubiana Julie, Dureab Fekri, Dhabaan Ghulam, Brisse Sylvain, NCPHL diphtheria outbreak working group, Lefrancq, Noemie [0000-0001-5991-6169], Salje, Henrik [0000-0003-3626-4254], Apollo - University of Cambridge Repository, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP), Centre national de Référence des Corynebactéries du Complexe Diphtheriae - National Reference Center Corynebacteria of the diphtheriae complex (CNR), National Centre of the Public Health Laboratories [Sana'a, Yemen], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Ministry of Public Health and Population [Sana'a, Yemen], Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Collège Doctoral, Sorbonne Université (SU), Vrije Universiteit Brussel (VUB), University of Cambridge [UK] (CAM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Akkon University of Human Sciences - Akkon Hochschule für Humanwissenschaften [Berlin, Allemagne], Universität Heidelberg [Heidelberg] = Heidelberg University, University of Toronto, This work was supported financially by institutional funding from the NCPHL (Sana'a, Yemen) and Institut Pasteur. The French National Reference Center for Corynebacteria of the diphtheriae complex received support from Institut Pasteur and Public Health France (Santé publique France, Saint Maurice, France). This work was also supported financially by the French Government Investissement d'Avenir Programme Laboratoire d'Excellence, Integrative Biology of Emerging Infectious Diseases (ANR-10-LABX-62-IBEID)., NCPHL diphtheria outbreak working group (Abdulaziz A Rawah, Mohammed A Aldawla, Ekram M AlAwdi, Nabila M AlMoalmy, Huda Z AlShami, Ali A AlSomainy), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Department of Clinical Microbiology, Brussels Heritage Lab, Supporting clinical sciences, Microbiology and Infection Control, Clinical Biology, Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], and Universität Heidelberg [Heidelberg]
Subjects: OHEJP, Yemen/epidemiology, Adult, Corynebacterium diphtheriae/genetics, Yemen, Adolescent, [SDV]Life Sciences [q-bio], genomic epidemiology, Corynebacterium, Diphtheria/epidemiology, Disease Outbreaks, Young Adult, Anti-Infective Agents, Humans, Diphtheria Toxin, Child, Phylogeny, Aged, Aged, 80 and over, Diphtheria Toxin/genetics, Corynebacterium diphtheriae, Infant, Diphtheria, Codes4strains, Genomics, Middle Aged, Cross-Sectional Studies, Child, Preschool
Abstract: Background An outbreak of diphtheria, declared in Yemen in October, 2017, is ongoing. We did a cross-sectional study to investigate the epidemiological, clinical, and microbiological features of the outbreak. Methods Probable cases of diphtheria that were defined clinically and recorded through a weekly electronic diseases early warning system (from 2017, week 22, to 2020, week 17) were used to identify trends of the outbreak (we divided the epidemic into three time periods: May 29, 2017, to June 10, 2018; June 11, 2018, to June 3, 2019; and June 4, 2019, to April 26, 2020). We used the line list of diphtheria reports for governorate-level descriptions. Vaccination coverage was estimated using the 2017 and 2018 annual reports by the national Expanded Programme on Immunization. To confirm cases biologically,Corynebacterium diphtheriaewas isolated and identified from throat swabs using standard microbiological culture and identification procedures. We assessed differences in the temporal and geographical distributions of cases, including between different age groups. For in-depth microbiological analysis,toxgene and species-specificrpoBreal-time PCR, Illumina genomic sequencing, antimicrobial susceptibility analysis (disk diffusion, E-test), and the Elek diphtheria toxin production test were done on confirmed cases. We used genomic data for phylogenetic analyses and to estimate the nucleotide substitution rate. Findings The Yemen diphtheria outbreak affected almost all governorates (provinces), with 5701 probable cases and 330 deaths recorded up to April 26, 2020. We collected clinical data for 888 probable cases with throat swab samples referred for biological confirmation, and genomic data for 42 positive cases, corresponding to 43 isolates (two isolates from one culture were included due to distinct colony morphologies). The median age of patients was 12 years (range 0·2–80). The proportion of cases in children aged 0–4 years was reduced during the second time period, after a vaccination campaign, compared with the first period (19% [95% CI 18–21] in the first periodvs14% [12–15] in the second period, pC diphtheriaephylogenetic sublineages, four of which are genetically related to isolates from Saudi Arabia, Eritrea, and Somalia. Inter-sublineage genomic variations in genes associated with antimicrobial resistance, iron acquisition, and adhesion were observed. The predominant sublineage (30 [70%] of 43 isolates) was resistant to trimethoprim and was associated with unique genomic features, more frequent neck swelling (p=0·0029) and a younger age of patients (p=0·060) compared with the other sublineages. Its evolutionary rate was estimated at 1·67 × 10−6substitutions per site per year, placing its most recent common ancestor in 2015, and indicating silent circulation ofC diphtheriaein Yemen before the outbreak was declared. Interpretation In the Yemen outbreak,C diphtheriaeshows high phylogenetic, genomic, and phenotypic variation. Laboratory capacity and real-time microbiological monitoring of diphtheria outbreaks need to be scaled up to inform case management and transmission control of diphtheria. Catch-up vaccination might have provided some protection to the targeted population (children aged 0–4 years). Funding National Centre of the Public Health Laboratories (Yemen), Institut Pasteur, and the French Government Investissement d'Avenir Programme. Translation For the Arabic translation of the abstract see Supplementary Materials section.
Published: 2021
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249. Education and mental health: good reasons to vaccinate children

Author: Arnaud Fontanet, Simon Cauchemez, Violette Mouro, Cécile Tran Kiem, Angèle Consoli, Paolo Bosetti, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral, Sorbonne Université (SU), Ministère des Solidarités et de la Santé [Paris, France], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Abord dimensionnel des épisodes psychotiques de l’enfant et de l’adolescent: implications génétiques, métaboliques et auto-immunes, Groupe de recherche clinique Troubles psychiatriques et développement (GRC 15 - PSYDEV), Sorbonne Université (SU)-Sorbonne Université (SU), 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), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), We declare funding from Investissement d'Avenir programme, the Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases programme, and the EU's Horizon 2020 research and innovation programme., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Abord dimensionnel des épisodes phychotiques de l'enfant et de l'adolescent : implications génétiques, métaboliques et auto-immunes (PSYDEV), and Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], MEDLINE, 030204 cardiovascular system & hematology, Education, 03 medical and health sciences, 0302 clinical medicine, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], MESH: Child, Correspondence, medicine, Humans, 030212 general & internal medicine, Child, ComputingMilieux_MISCELLANEOUS, MESH: Humans, business.industry, MESH: Mental Health, Vaccination, MESH: Education, MESH: Patient Acceptance of Health Care, General Medicine, MESH: Vaccination, Patient Acceptance of Health Care, Mental health, Mental Health, MESH: COVID-19 Vaccines, Family medicine, business
Abstract: International audience
Published: 2021
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250. DHA-containing phospholipids control membrane fusion and transcellular tunnel dynamics

Author: Meng-Chen Tsai, Lucile Fleuriot, Sébastien Janel, David Gonzalez-Rodriguez, Camille Morel, Amel Mettouchi, Delphine Debayle, Stéphane Dallongeville, Jean-Christophe Olivo-Marin, Bruno Antonny, Frank Lafont, Emmanuel Lemichez, Hélène Barelli, 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, 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), 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), Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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, ANR 10-EQPX-04-01, ANR-10-INBS-04 and ANR-10-LABX-62-IBEID) and FEDER 12001407, and partially by grants from the France-BioImaging infrastructure (ANR-10-INBS-04) and the Labex IBEID (ANR-10-LABX-62-IBEID). M.-C.T. 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-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), 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, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID
Subjects: Docosahexaenoic Acids, Transendothelial cell macroaperture, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Membrane Fusion, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Animals, Humans, Endothelium, Large-scale membrane dynamics, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Phospholipids, Polyunsaturated phospholipids, Actin cytoskeleton, Cell Membrane, Endothelial Cells, Cell Biology, Bacterial toxin, [SDV] Life Sciences [q-bio], DHA, Docosahexaenoic acid, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, lipids (amino acids, peptides, and proteins)
Abstract: Metabolic studies and animal knockout models point to the critical role of polyunsaturated docosahexaenoic acid (22:6, DHA)-containing phospholipids (DHA-PLs) in physiology. Here, we investigated the impact of DHA-PLs on the dynamics of transendothelial cell macroapertures (TEMs) triggered by RhoA inhibition-associated cell spreading. Lipidomic analyses showed that human umbilical vein endothelial cells (HUVECs) subjected to a DHA diet undergo a 6-fold enrichment in DHA-PLs at the plasma membrane (PM) at the expense of monounsaturated oleic acid-containing PLs (OA-PLs). Consequently, DHA-PL enrichment at the PM induces a reduction in cell thickness and shifts cellular membranes towards a permissive mode of membrane fusion for transcellular tunnel initiation. We provide evidence that a global homeostatic control of membrane tension and cell cortex rigidity minimizes overall changes of TEM area through a decrease of TEM size and lifetime. Conversely, low DHA-PL levels at the PM lead to the opening of unstable and wider TEMs. Together, this provides evidence that variations of DHA-PL levels in membranes affect cell biomechanical properties.
Published: 2021
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