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1. Molecular and Phylogenetic Analyses of 16 Novel Simian T Cell Leukemia Virus Type 1 from Africa: Close Relationship of STLV-1 from Allenopithecus nigroviridis to HTLV-1 Subtype B Strains

Author: Meertens, Laurent, Rigoulet, Jacques, Mauclère, Philippe, Van Beveren, Monique, Chen, Guo Min, Diop, Ousmane, Dubreuil, Guy, Georges-Goubot, Marie-Claude, Berthier, Jean-Luc, Lewis, John, and Gessain, Antoine
Published: 2001
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2. Differentiation-dependent susceptibility of human muscle cells to Zika virus infection

Author: Gillian Butler-Browne, Jim Zoladek, Ingo Riederer, Quentin Giai Gianetto, Philippe Roingeard, Patricia Jeannin, Julien Burlaud-Gaillard, Pierre-Emmanuel Ceccaldi, Mariette Matondo, Valérie Choumet, Thibault Chaze, Vincent Legros, Vincent Mouly, Philippe V. Afonso, Antoine Gessain, Mariela-Natacha Gonzàlez, Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Plateforme IBISA de Microscopie Electronique [CHRU de Tours] (UNIV Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Université de Tours, Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Centre National de la Recherche Scientifique (CNRS)-Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris]-Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre de recherche en myologie, Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris], This work was supported by a Pasteur-Fiocruz grant. VL was supported by a fellowship from the 'Fondation pour la Recherche Médicale' (FRM), IR and MG by CNPq/Ciências sem Fronteiras program, CNPq/Brazilian National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM). FOCEM - Mercosur Structural Convergence Fund 03/11. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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), Institut Pasteur [Paris] (IP), Matondo, Mariette, Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), UMRS974, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche en Myologie, 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), and Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ)
Subjects: Proteomics, Pulmonology, RC955-962, Apoptosis, Pathology and Laboratory Medicine, Zika virus, 0302 clinical medicine, Medical Conditions, Animal Cells, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Arctic medicine. Tropical medicine, MESH: Proteins, Chikungunya, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Zika Virus Infection, Stem Cells, MESH: Proteomics, 3. Good health, Medical Microbiology, Arboviral Infections, Viral Pathogens, Interferon Type I, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Public aspects of medicine, Cellular Types, MESH: Zika Virus, Microbiology, 03 medical and health sciences, Respiratory Disorders, MESH: Zika Virus Infection, Humans, Microbial Pathogens, MESH: Humans, Flaviviruses, MESH: Host-Pathogen Interactions, Public Health, Environmental and Occupational Health, Organisms, Biology and Life Sciences, Chikungunya Infection, Proteins, medicine.disease, Tropical Diseases, Virology, MESH: Cell Line, 030104 developmental biology, Biological Tissue, Interferon type I, Developmental Biology, 0301 basic medicine, RNA viruses, MESH: Cell Death, MESH: Interferon Type I, MESH: Muscle Cells, Viral Diseases, [SDV]Life Sciences [q-bio], Muscle Fibers, Skeletal, medicine.disease_cause, Virus Replication, Dengue fever, Myoblasts, Cytopathogenic Effect, Viral, Medicine and Health Sciences, Morphogenesis, Myocyte, Cytopathic effect, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Muscle Fibers, Skeletal, Cell Death, Myogenesis, Cell Differentiation, Muscle Differentiation, Infectious Diseases, Cell Processes, Viruses, Host-Pathogen Interactions, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Disease Susceptibility, Stem cell, RA1-1270, Pathogens, Anatomy, medicine.drug, Research Article, Neglected Tropical Diseases, MESH: Cell Differentiation, 030231 tropical medicine, Muscle Tissue, MESH: Disease Susceptibility, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Stem Cells, Biology, Cell Line, medicine, MESH: Myoblasts, Muscle Cells, MESH: Virus Replication, Cell Biology, Zika Virus, biology.organism_classification, MESH: Cytopathogenic Effect, Viral, Respiratory Infections
Abstract: Muscle cells are potential targets of many arboviruses, such as Ross River, Dengue, Sindbis, and chikungunya viruses, that may be involved in the physiopathological course of the infection. During the recent outbreak of Zika virus (ZIKV), myalgia was one of the most frequently reported symptoms. We investigated the susceptibility of human muscle cells to ZIKV infection. Using an in vitro model of human primary myoblasts that can be differentiated into myotubes, we found that myoblasts can be productively infected by ZIKV. In contrast, myotubes were shown to be resistant to ZIKV infection, suggesting a differentiation-dependent susceptibility. Infection was accompanied by a caspase-independent cytopathic effect, associated with paraptosis-like cytoplasmic vacuolization. Proteomic profiling was performed 24h and 48h post-infection in cells infected with two different isolates. Proteome changes indicate that ZIKV infection induces an upregulation of proteins involved in the activation of the Interferon type I pathway, and a downregulation of protein synthesis. This work constitutes the first observation of primary human muscle cells susceptibility to ZIKV infection, and differentiation-dependent restriction of infection from myoblasts to myotubes. Since myoblasts constitute the reservoir of stem cells involved in reparation/regeneration in muscle tissue, the infection of muscle cells and the viral-induced alterations observed here could have consequences in ZIKV infection pathogenesis., Author summary Muscle cells are potential targets of many arboviruses, such as Ross River, Dengue, Sindbis, and chikungunya viruses, and may be involved in the disease manifestation. During the recent outbreak of Zika virus (ZIKV), myalgia was one of the most frequently reported symptoms. We investigated the susceptibility of human muscle cells to ZIKV infection. Using an in vitro model of human muscle stem cells (myoblasts) that can be differentiated into differentiated muscle cells (myotubes), we found that myoblasts can be infected by ZIKV. In contrast, myotubes were shown to be resistant to ZIKV infection. Infection induced the death of infected cells. Protein levels 24h and 48h post-infection indicate that ZIKV infection induces an upregulation of proteins involved in the activation of the Interferon type I pathway, and a downregulation of protein synthesis. This work constitutes the first observation of primary human muscle cells susceptibility to ZIKV infection, muscle stem cells being susceptible while differentiated muscle cells are resistant. Since myoblasts constitute the reservoir of stem cells involved in reparation/regeneration in muscle tissue, the infection of muscle cells and the viral-induced alterations observed here could have consequences during ZIKV infection.
Published: 2020

3. Proteomic analysis of plasma extracellular vesicles reveals mitochondrial stress upon HTLV-1 infection

Author: Philippe V. Afonso, Antoine Gessain, Quentin Giai Gianetto, Olivier Gout, Mariette Matondo, Patricia Jeannin, Thibault Chaze, Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], This work was supported by Ville de Paris [Programme Emergence(s)] and Ligue Contre le Cancer/Comité de Paris (RS18/75-5)., We would like to thank Camille Roesch (Izon) for her help in measuring the samples composition, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology ( UTechS MSBio ), Centre de Bioinformatique, Biostatistique et Biologie Intégrative ( C3BI ), Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), and Institut Pasteur [Paris]-Institut Pasteur [Paris]
Subjects: Adult, Male, Proteomics, 0301 basic medicine, Science, Disease, Mitochondrion, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Mass Spectrometry, Article, Mitochondrial Proteins, Pathogenesis, Extracellular Vesicles, Young Adult, 03 medical and health sciences, Retrovirus, Stress, Physiological, immune system diseases, hemic and lymphatic diseases, Humans, Aged, Human T-lymphotropic virus 1, Multidisciplinary, biology, Proteins, virus diseases, Neurodegenerative Diseases, Middle Aged, biology.organism_classification, HTLV-I Infections, Lymphoproliferative Disorders, 3. Good health, Mitochondria, 030104 developmental biology, Viral infection, Carrier State, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chromatography, Gel, Biomarker (medicine), Medicine, Female, HTLV-1 Infection, Lysosomes, Asymptomatic carrier, Biomarkers, Intracellular
Abstract: Extracellular vesicles (EVs) can participate in intercellular communication and pathogenesis. EVs contain many cargos, including proteins, and the composition of EVs differs between cell-types and activation levels. Thus, plasma EVs can be used as a biomarker of systemic response to infection and/or disease progression. In this study, we aimed at describing alterations in the protein content of plasma EVs upon infection with the human T-lymphotropic retrovirus type 1 (HTLV-1). HTLV-1 is the etiological agent of a lymphoproliferative disease (ATL) and a series of inflammatory diseases, including a neurodegenerative inflammatory disease (HAM/TSP). We found that plasma EVs are more abundant and smaller in HTLV-1 asymptomatic carriers or HAM/TSP patients when compared to uninfected healthy donors. Moreover, EVs from HTLV-1 infected donors contain markers of metabolic and mitochondrial stress.
Published: 2018

4. Trichodysplasia spinulosa polyomavirus infection occurs during early childhood with intra-familial transmission, especially from mother to child

Author: Patricia Tortevoye, Antoine Gessain, Jérôme T. J. Nicol, Pierre Coursaget, Vincent Pedergnana, Claire Martel-Jantin, Laurent Abel, Valérie Leblond, Antoine Touzé, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), UMR3569, Centre National de la Recherche Scientifique (CNRS), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], French Government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' grant no. 136 ANR-10-LABX-62-IBEID, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], UR Infectiologie animale et Santé publique (UR IASP), Institut National de la Recherche Agronomique (INRA), St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, rockefeller university, Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), University of Oxford, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Virologie (CNRS - UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Wellcome Trust Centre for Human Genetics, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique ( CNRS ), UR Infectiologie animale et Santé publique ( UR IASP ), and Institut National de la Recherche Agronomique ( INRA )
Subjects: 0301 basic medicine, Male, Familial Study, [SDV]Life Sciences [q-bio], Merkel cell polyomavirus, étude séro-épidémiologique, Biochemistry, 030207 dermatology & venereal diseases, 0302 clinical medicine, infection virale, cameroun, Seroepidemiologic Studies, Odds Ratio, Early childhood, Cameroon, Child, Transmission (medicine), Trichodysplasia spinulosa polyomavirus, Age Factors, Intrafamilial transmission, 3. Good health, Correlation, Child, Preschool, Female, Adult, Mother to child transmission, Adolescent, polyomavirus, Mothers, Dermatology, Biology, Skin Diseases, Antibodies, maladie cutanée, 03 medical and health sciences, Young Adult, Primary infection, Humans, Molecular Biology, Polyomavirus Infections, [ SDV ] Life Sciences [q-bio], Transmission mode, Infant, Newborn, Infant, Cell Biology, transmission maternelle, biology.organism_classification, Virology, Infectious Disease Transmission, Vertical, 030104 developmental biology, Hair Diseases
Abstract: International audience; To get new insights into the distribution and modes of acquisition of trichodysplasia spinulosa polyomavirus (TSPyV) infection, we performed a seroepidemiological study in two populations from Cameroon. Our results suggest that TSPyV infection occurs, through close contacts, during early childhood with intra-familial transmission, especially from mother to child.
Published: 2017

5. Gag-specific CD8 T-cell proliferation is associated with higher peripheral blood levels of TGF-β and gut-homing T cells in youths perinatally infected with HIV-1 – The ANRS- EP38-IMMIP Study

Author: Warszawski, Josiane, Avettand-Fenoel, Véronique, Rouzioux, Christine, Scott-Algara, Daniel, Montange, Thomas, Didier, Céline, Le Chenadec, Jérôme, Viard, Jean-Paul, Dollfus, Catherine, Blanche, Stéphane, Buseyne, Florence, Université Paris-Sud - Paris 11 (UP11), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) - Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Paul Brousse - Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Cytokines et Inflammation, Institut Pasteur [Paris], Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), Mécanismes de l'Hérédité épigénétique, Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP), Service d'Hématologie et Oncologie pédiatriques, Hôpital Trousseau [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Trousseau [APHP], Service d'immunologie, hématologie et rhumatologie pédiatriques [CHU Necker], This work was supported by the 2006-232 and 2009-165 grants from the 'Agence Nationale de Recherche sur le SIDA et les Hépatites' (ANRS, www.anrs.fr) and by the 'Fondation AREVA' (http://www.areva.com/FR/groupe-910/fondation-implication-societale-pour-un-developpement-durable.html)., ANRS-EP38-IMMIP, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Mécanismes de l'Hérédité épigénétique / Mechanisms of epigenetic inheritance, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'immuno-hématologie pédiatrique [CHU Necker], Peptides were provided by the National Institutes of Health AIDS Research and Reference Reagent Program. We thank all the patients who agreed to participate in this study. We also thank the nurses and staff members from the various clinical sites. We thank Sandrine Leveillé (Hôpital Robert Debré), Geneviève Vaudre (Hôpital Trousseau), Sylvie Tassi (Hôpital Jean Verdier), Nora Boudjoudi (Hôpital Port Royal), Marie-Christine Mourey (Hôpital Necker), Thierry Wack (CESP INSERM U1018), Yassine Benmebarek, and Naima Bouallag-Bonnet (former members of CESP INSERM U1018). We thank Yves Rivière for his role in this collaborative work. We also thank Elisabeth Monchâtre, Pauline Louche, and Céline Clairet for expert technical assistance., Buseyne, Florence, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, perinatal infection, HIV, CD8 T cells, immune activation, regulatory T cells, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, mucosal immunity, adolescents
Abstract: International audience; Background: Gag-specific T lymphocytes play a key role in the control of HIV replication. Their restoration will be important for future reservoir targeting strategies. Here, we aimed to identify immune correlates of Gag-specific CD8 T-cell proliferation in youths with perinatally acquired HIV-1 infection. Methods: The ANRS-EP38-IMMIP study included youths of 15 to 24 years of age. Fifty-three were taking cART and aviremic at the time of the study and had undergone valid CFSE-based flow cytometry T-cell proliferation assays. Plasma analytes were quantified by ELISA or multiplex assays. Peripheral blood cells were phenotyped by flow cytometry. Logistic regression was used to study the association between Gag-specific T-cell proliferation and immune markers. Results: Patients with Gag-specific CD8 T-cell proliferation had higher levels of plasma TGF-β1, a lower proportion of naive cells among Tregs, and higher percentages of CD4 and CD8 T cells expressing the α4β7 integrin or CD161 molecule than those without a Gag-specific response. These associations were significant based on analyses including potential confounders. Conclusion: Preserved Gag-specific CD8 T-cell proliferation was associated with higher TGF-β1 levels and increased percentages of T cells with a gut-homing phenotype at least 15 years after HIV infection during the perinatal period.
Published: 2016

6. Adult T cell leukemia aggressivenness correlates with loss of both 5-hydroxymethylcytosine and TET2 expression

Author: Olivier Hermine, Philippe Gaulard, Patrice Dubreuil, Katia Hanssens, Laetitia Waast, Claudine Pique, Vahid Asnafi, Felipe Suarez, Antoine Gessain, Ambroise Marçais, Julie Bruneau, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Département de Pathologie [CHU Necker], Université Paris Descartes - Paris 5 ( UPD5 ) -Université Sorbonne Paris Cité ( USPC ) -CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie de Marseille ( CRCM ), Aix Marseille Université ( AMU ) -Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), This study was supported by grants from the Institut National du Cancer (INCA PL Bio), INSERM (plan cancer) and Ligue Nationale contre le Cancer (Equipe labélisée OH and PD). AM was the recipient of a doctoral fellowship from INCA., Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), and Bos, Mireille
Subjects: Population, T-cell leukemia, Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, DNA hydroxymethylation, Downregulation and upregulation, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Allele, education, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 5-Hydroxymethylcytosine, education.field_of_study, T-cells, leukemia, ten eleven translocation, medicine.disease, Molecular biology, Lymphoma, retrovirus, Leukemia, Oncology, chemistry, 030220 oncology & carcinogenesis, DNA methylation, Research Paper, 030215 immunology
Abstract: International audience; Mutations in TET2, encoding one of the TET members responsible for the conversion of DNA cytosine methylation to hydroxymethylation (5-hmc), have been recently described in Human T-lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma (ATLL). However, neither the amount of genomic 5-hmc in ATLL tumor cells nor TET2 expression has been studied yet. In this study, we analyzed these two parameters as well as the mutational status of TET2 in ATLL patients. By employing a direct in situ approach, we documented that tumor T cells infiltrating lymph nodes exhibit low level of 5-hmc compared to residual normal T cells. Furthermore, this 5-hmc defect was more pronounced in tumor T cells from acute patients than from chronic ones and correlated with reduced expression of TET2 protein. TET2 variations were found in 14 patients (20%), including 13 with aggressive forms. Strikingly, 9 of the 14 patients showed the same variation (SNP rs72963007), whose frequency in ATLL patients was significantly higher than that of an ethnically matched control population (13% vs. 5%). However, no reduction of 5-hmc was found in PBMC from individuals possessing the variant rs72963007 TET2 allele, as compared to wild-type individuals. In contrast, a robust correlation was observed between 5-hmc and the levels of TET2 mRNA. Finally, loss of 5-hmc and TET2 downregulation both correlated with poor survival. These findings demonstrate that ATLL progression coincides with loss of genomic 5-hmc and indicate that downregulation of TET2, rather than TET2 mutations, is the key mechanism involved in 5-hmc modulation during ATLL progression.
Published: 2016

7. Human T-Lymphotropic Virus Type 1-Induced Overexpression of Activated Leukocyte Cell Adhesion Molecule (ALCAM) Facilitates Trafficking of Infected Lymphocytes through the Blood-Brain Barrier

Author: Philippe V. Afonso, Olivier Gout, Thomas Montange, Antoine Gessain, Danielle Seilhean, Luis Cartier, Florent Percher, Pierre-Emmanuel Ceccaldi, Patricia Jeannin, Céline Curis, Pierre-Olivier Couraud, Sébastien A Chevalier, Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Oncogenèse rétrovirale – Retroviral Oncogenesis (OR), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Departamento de Ciencias Neurologicas, Facultad de Medicina, Universidad de Chile, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], This work, including the efforts of Philippe V Afonso, was funded by Ville de Paris (Emergence). This work, including the efforts of Florent Percher, was funded by Region Ile de France (DIMMALINF).This work, including the efforts of Celine Curis, was funded by Ministère de l’Education Nationale (Ministry of Education, France), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 ( UPD7 ) -PRES Sorbonne Paris Cité, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre International de Recherche en Infectiologie ( CIRI ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Afonso, Philippe
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, CD4-Positive T-Lymphocytes, Fetal Proteins, 0301 basic medicine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 0302 clinical medicine, Cell Movement, immune system diseases, Tropical spastic paraparesis, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Human T-lymphotropic virus 1, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Tight junction, NF-kappa B, Activated-Leukocyte Cell Adhesion Molecule, virus diseases, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Gene Products, tax, Virus-Cell Interactions, 3. Good health, medicine.anatomical_structure, Blood-Brain Barrier, Blood brain barrier, 030220 oncology & carcinogenesis, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Host-Pathogen Interactions, Cell Adhesion Molecules, Neuronal, Immunology, Central nervous system, Blood–brain barrier, Microbiology, Cell Line, 03 medical and health sciences, Antigens, CD, Virology, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Humans, ALCAM, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Endothelial Cells, medicine.disease, biology.organism_classification, 030104 developmental biology, HTLV-1, Insect Science, Cancer research, Immunoglobulin superfamily, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease develops upon infiltration of HTLV-1-infected lymphocytes into the central nervous system, mostly the thoracic spinal cord. The central nervous system is normally protected by a physiological structure called the blood-brain barrier (BBB), which consists primarily of a continuous endothelium with tight junctions. In this study, we investigated the role of activated leukocyte cell adhesion molecule (ALCAM/CD166), a member of the immunoglobulin superfamily, in the crossing of the BBB by HTLV-1-infected lymphocytes. We demonstrated that ALCAM is overexpressed on the surface of HTLV-1-infected lymphocytes, both in chronically infected cell lines and in primary infected CD4 + T lymphocytes. ALCAM overexpression results from the activation of the canonical NF-κB pathway by the viral transactivator Tax. In contrast, staining of spinal cord sections of HAM/TSP patients showed that ALCAM expression is not altered on the BBB endothelium in the context of HTLV-1 infection. ALCAM blockade or downregulation of ALCAM levels significantly reduced the migration of HTLV-1-infected lymphocytes across a monolayer of human BBB endothelial cells. This study suggests a potential role for ALCAM in HAM/TSP pathogenesis. IMPORTANCE Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease is the consequence of the infiltration of HTLV-1-infected lymphocytes into the central nervous system (CNS), mostly the thoracic spinal cord. The CNS is normally protected by a physiological structure called the blood-brain barrier (BBB), which consists primarily of a continuous endothelium with tight junctions. The mechanism of migration of lymphocytes into the CNS is unclear. Here, we show that the viral transactivator Tax increases activated leukocyte cell adhesion molecule (ALCAM/CD166) expression. This molecule facilitates the migration of lymphocytes across the BBB endothelium. Targeting this molecule could be of interest in preventing or reducing the development of HAM/TSP.
Published: 2016

8. Gag-specific CD4 T-cell proliferation, plasmacytoid dendritic cells and ethnicityin perinatally HIV-1-infected youths – The ANRS-EP38-IMMIP Study Short title: T-cell proliferation and dendritic cells

Author: Scott-Algara , Daniel, Warszawski , Josiane, Le Chenadec , Jérôme, Didier , Céline, Montange , Thomas, Viard , Jean-Paul, Dollfus , Catherine, Avettand-Fenoel , Véronique, Rouzioux , Christine, Blanche , Stéphane, Buseyne , Florence, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Mécanismes de l'Hérédité épigénétique / Mechanisms of epigenetic inheritance, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Virologie [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), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], ANRSFondation AREVA, ANRS-EP38-IMMIP, Buseyne, Florence, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Mécanismes de l'Hérédité épigénétique, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Epidémiologie et Physiopathologie des Virus Oncogènes, Assistance publique - Hôpitaux de Paris (AP-HP), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) ( EA 7327 ), Université Paris Descartes - Paris 5 ( UPD5 ), Service d'Hématologie et Oncologie pédiatriques, Hôpital Trousseau [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP]
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, T-cell proliferation, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, CD4 T cells, [ SDV.IMM.IA ] Life Sciences [q-bio]/Immunology/Adaptive immunology, sCD14, perinatal HIV infection, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, youths, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, dendritic cells
Abstract: International audience; In perinatally HIV-1-infected youths living in France, we previously reported that Gag-specific CD4 and CD8 T-cell proliferation is more frequently detected in patients of black ethnicity than in those of other ethnicities. We observed that black patients had higher levels of dendritic cells than other patients. We aimed to study the association of dendritic cell levels with Gag-specific T-cell proliferation. The ANRS-EP38-IMMIP study is an observational study of youths aged between 15 and 24 years who were perinatally infected with HIV. A single blood sample was drawn for virological and immunological assays. Data from cART treated 53 youths with undetectable plasma HIV RNA were analyzed. Gag-specific T-cell proliferation was assessed using a CFSE-based test. Peripheral blood myeloid and plasmacytoid dendritic cells (mDCs and pDCs) were phenotyped by flow cytometry. Plasma markers were quantified by ELISA or multiplex assays. Logistic regression was used for univariate and multivariate analyses. Patients with Gag-specific CD4 T-cell proliferative responses had significantly higher percentages and absolute counts of mDCs and pDCs in the peripheral blood than nonresponding patients. Gag-specific CD4 and CD8 T-cell proliferation were associated with lower plasma sCD14 levels. Plasma levels of IFN-α, TRAIL and chemokines involved in T-cell migration to secondary lymphoid organs were not associated with T-cell proliferation. Multivariate analysis confirmed the association between Gag-specific CD4 T-cell proliferation and pDC levels. In conclusion, dendritic cell levels are a robust correlate of the presence of Gag-specific T-cell proliferation in successfully treated youths.
Published: 2016

9. Traitement précoce des nourrissons vivant avec le VIH-1

Author: Frange, Pierre, Avettand-Fenoël, Véronique, Buseyne, Florence, 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), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Microbiologie Clinique, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) ( EA 7327 ), Université Paris Descartes - Paris 5 ( UPD5 ), Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], and Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, antiretroviral therapy, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, early treatment, enfants, [ SDV.IMM.IA ] Life Sciences [q-bio]/Immunology/Adaptive immunology, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, children, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, traitement précoce, antirétroviraux, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, VIH-1
Abstract: International audience; HIV-1 infection has several distinctive features in children compared to adults, especially (i) the occurrence of the primary infection during a period of high vulnerability because of the immaturity of the immune system, which partly explains that around 15% of children experience a rapidly unfavourable clinical course with death before 3-4 years-of-age (in the absence of antiretroviral therapy (ART)), and (ii) the capacity of immune restoration under ART is higher in children than in adults, which is probably partly explained by an improved thymic activity. Thus, it has recently been suggested that early ART initiation in HIV-1-infected children could protect the immune system from HIV-induced damages during the critical period of immunological immaturity. This “protective” effect could have a long-term impact, partly because specific immune responses against HIV could be developed more efficiently in case of later re-exposure to HIV viremia. Finally, early ART initiation could also have virological benefits, because of the drastic reduction of the size of the viral reservoir.; L'infection à VIH-1 présente deux spécificités majeures chez l'enfant par rapport à l'adulte. La première est la présence d'une forme très rapide de la maladie chez environ 15% des nourrissons qui connaissent une évolution précoce vers la forme SIDA avec décès avant l'âge de 3-4 ans (en l'absence de traitement antiviral). Cette évolution s'explique par l'immaturité du système immunitaire des nourrissons, qui rend leur organisme particulièrement vulnérable aux dommages causés par le virus. La seconde spécificité est que, sous traitement antiviral, la restauration des défenses immunitaires des enfants est bien meilleure que celle observée chez les adultes. L'instauration systématique d'une multithérapie antirétrovirale dès les premiers mois de vie a un bénéfice indiscutable en terme de mortalité néonatale. Elle pourrait également apporter un bénéfice à long terme, en limitant rapidement la constitution du réservoir viral et en protégeant le système immunitaire des nourrissons des dommages viro-induits.
Published: 2016

10. Epidemiological Evidence of Nosocomial and Zoonotic Transmission of Human T-Cell Leukemia Virus-1 in a Large Survey in a Rural Population of Central Africa

Author: Jill-Léa Ramassamy, Chanceline Bilounga Ndongo, Patrick Nnuka, Maëlle Antunes, Margot Le Mener, Edouard Betsem a Betsem, Richard Njouom, Olivier Cassar, Arnaud Fontanet, Antoine Gessain, 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), Ministère de la Santé Publique [Yaoundé, Cameroun], Université de Douala, Université de Yaoundé I, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), 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), This work was supported by the European Union as part of the EboSursy project (grant number FOOD/2016/379-660 to J. L. R.), and the Institut Pasteur, France and the Centre National de la Recherche Scientifique, UMR 3569, through the Investissement d’Avenir as part of a Laboratoire d’Excellence French research program, Integrative Biology of Emerging Infectious Diseases (grant number ANR10-LBX- 62 IBEID to A. G.). Funding to pay the Open Access publication charges for this article was provided by the European Union., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: Infectious Diseases, HTLV-1, [SDV]Life Sciences [q-bio], Immunology and Allergy, Cameroon HTLV-1 central Africa cross-sectional survey epidemiology nosocomial zoonoses, epidemiology, nosocomial, Cameroon, central Africa, cross-sectional survey, zoonoses
Abstract: Background Central Africa is one of the largest areas of high endemicity for human T-cell leukemia virus-1 (HTLV-1). However, no preventive measures are yet implemented to reduce its transmission, which can be sexual, from mother-to-child, or through contaminated blood products. Rare zoonotic transmissions from nonhuman primates (NHPs) have also been reported in this region. Here we investigated the HTLV-1 prevalence and associated risk factors in a rural population in Cameroon. Methods From 2019 to 2021, we performed a cross-sectional survey in the eastern region of Cameroon. HTLV-1 infection was first screened by ELISA, then tested by western blot and envelope gene targeted polymerase chain reaction. Risk factors associated with HTLV-1 infection were identified by logistic regression in univariable and multivariable analyses. Results Among 3400 participants, HTLV-1 prevalence was 1.1% (95% confidence interval [CI], .7–1.5). Factors independently associated with HTLV-1 infection were Pygmy ethnicity (adjusted odd ratio [aOR], 2.9; 95% CI, 1.3–6.2), history of surgery (aOR, 6.3; 95% CI, 2.2–17.8), and NHP bite (aOR, 6.6; 95% CI, 2.2–19.8). Conclusions These results suggest both iatrogenic and zoonotic transmission of HTLV-1 in Cameroon. Further studies are needed to assess the risk of nosocomial transmission of HTLV-1, to guide public health authorities in implementing preventive measures to control HTLV-1 transmission.
Published: 2022

11. Identifying the Most Probable Mammal Reservoir Hosts for Monkeypox Virus Based on Ecological Niche Comparisons

Author: Manon Curaudeau, Camille Besombes, Emmanuel Nakouné, Arnaud Fontanet, Antoine Gessain, Alexandre Hassanin, 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), 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), 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), Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), and This project was supported by the French Agence Nationale de Recherche (ANR 2019 CE-35) and SCOR Corporate Foundation for Science.
Subjects: Monkeypox, animal reservoir, ecological niche model, tropical Africa, evergreen forests, Sciuridae, Infectious Diseases, [SDV]Life Sciences [q-bio], Virology
Abstract: BackgroundPrevious human cases or epidemics have suggested that Monkeypox virus (MPXV) can be transmitted through contacts with animals of African rainforests. Although MPXV has been identified in many mammal species, most are likely secondary hosts and the reservoir host has yet to be discovered.Methodology/Principal FindingsIn this study, we provide the full list of African mammal genera (and species) in which MPXV was previously detected and predict the geographic distributions of all species of these genera based on museum specimens and an ecological niche modelling (ENM) method. Then, we reconstruct the ecological niche of MPXV using georeferenced data on animal MPXV sequences and human index cases, and conduct overlap analyses with the ecological niches inferred for 99 mammal species in order to identify the most probable animal reservoir.Conclusions/SignificanceOur results show that the MPXV niche covers three African rainforests, the Congo Basin and Upper and Lower Guinean forests. The four mammal species showing the best niche overlap with MPXV are all arboreal rodents, including three squirrels,Funisciurus anerythrus, Funisciurus pyrropus, andHeliosciurus rufobrachium, andGraphiurus lorraineus. We conclude that the most probable MPXV reservoir isF. anerythrusbased on two niche overlap metrics, the areas of higher probabilities of occurrence, and available data on MPXV detection.SummaryMonkeypox (MPX) is an emerging zoonotic disease, endemic to rainforests of West and Central Africa, which manifests as a fever, swollen lymph nodes, and fatigue, followed by a rash with macular lesions progressing from papules to vesicles, pustules and scabs, usually on the face, hands, and feet for two to four weeks. The case fatality rate ranges from 1-3% in West Africa to 5-10% in Central Africa. The disease has been reported in 10 African countries between 1970 and today, with an increasing number of cases over the last decades and several exportations outside the continent, the last one in 2022 resulting in an epidemic involving mostly men who have sex with men, with more than 80,000 cases detected worldwide.Although MPX virus has been identified in many mammal species, most are likely secondary hosts and the reservoir host has yet to be discovered. In this study, we compare the predicted geographic distribution (ecological niche) of the MPX virus with that of 99 mammal species, and conclude that the most probable MPX reservoir is Thomas’s rope squirrel (Funisciurus anerythrus), followed by three other arboreal rodents, including two squirrels (Funisciurus pyrropusandHeliosciurus rufobrachium) and the Lorrain dormouse (Graphiurus lorraineus).
Published: 2023
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12. The crystal structure of a simian Foamy Virus receptor binding domain provides clues about entry into host cells

Author: Ignacio Fernández, Lasse Toftdal Dynesen, Youna Coquin, Riccardo Pederzoli, Delphine Brun, Ahmed Haouz, Antoine Gessain, Felix A. Rey, Florence Buseyne, Marija Backovic, Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Cristallographie (Plateforme) - Crystallography (Platform), This work was funded by the ‘Agence Nationale de la Recherche’ (ANR-10-LABX62-IBEID, Intra-Labex Grant, M.B.), the ‘Programme de recherche transversal from Institut Pasteur’ (PTR2020-353 ZOOFOAMENV, F.B.), and recurrent funding from Institut Pasteur (F.A.R, A.G.), We thank the staff from the Utechs Cytometry & Biomarkers and Crystallography platform at the Institut Pasteur, the synchrotron source SOLEIL (Saint-Aubin, France) for granting access to the facility, and to the staff of Proxima 1 and Proxima 2A beamlines for their kindness and assistance during X-ray data collections. We are grateful to Jan Hellert, Pablo Guardado-Calvo and Philippe Afonso for the discussions and advice, with special thanks to Max Baker for reading the manuscript and English language corrections., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: Multidisciplinary, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV]Life Sciences [q-bio], General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: The surface envelope glycoprotein (Env) of all retroviruses mediates virus binding to cells and fusion of the viral and cellular membranes. A structure-function relationship for the HIV Env that belongs to the Orthoretrovirus subfamily has been well established. Structural information is however largely missing for the Env of Foamy viruses (FVs), the second retroviral subfamily. FV Envs lack sequence similarity with their HIV counterpart. We present the X-ray structure of the receptor binding domain (RBD) of a simian FV Env at 2.6 Å resolution, revealing two subdomains and an unprecedented fold. We have generated a model for the organization of the RBDs within the trimeric Env which indicates that the upper subdomain is important for stabilization of the full-length Env, and have demonstrated that residues K342, R343, R359 and R369 in the lower subdomain play key roles in the interaction of the RBD and viral particles with heparan sulfate.
Published: 2023

13. Geographic distribution, clinical epidemiology and genetic diversity of the human oncogenic retrovirus HTLV-1 in Africa, the world’s largest endemic area

Author: Antoine Gessain, Jill-Léa Ramassamy, Philippe V. Afonso, 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), The French government’s 'Investissement d’Avenir' Program, Laboratoire d’Excellence (LabEx): 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LBX-62-IBEID) and the European Union as part of the EboSursy project (FOOD/2016/379-660)., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: MESH: ATL, [SDV]Life Sciences [q-bio], Immunology, MESH: HAM/TSP, MESH: Africa, MESH: Epidemiology, MESH: Genetic variability, HTLV-1, ATL, Africa, genetic variability, MESH: HTLV-1, Immunology and Allergy, epidemiology, HAM/TSP
Abstract: The African continent is considered the largest high endemic area for the oncogenic retrovirus HTLV-1 with an estimated two to five million infected individuals. However, data on epidemiological aspects, in particular prevalence, risk factors and geographical distribution, are still very limited for many regions: on the one hand, few large-scale and representative studies have been performed and, on the other hand, many studies do not include confirmatory tests, resulting in indeterminate serological results, and a likely overestimation of HTLV-1 seroprevalence. For this review, we included the most robust studies published since 1984 on the prevalence of HTLV-1 and the two major diseases associated with this infection in people living in Africa and the Indian Ocean islands: adult T-cell leukemia (ATL) and tropical spastic paraparesis or HTLV-1-associated myelopathy (HAM/TSP). We also considered most of the book chapters and abstracts published at the 20 international conferences on HTLV and related viruses held since 1985, as well as the results of recent meta-analyses regarding the status of HTLV-1 in West and sub-Saharan Africa. Based on this bibliography, it appears that HTLV-1 distribution is very heterogeneous in Africa: The highest prevalences of HTLV-1 are reported in western, central and southern Africa, while eastern and northern Africa show lower prevalences. In highly endemic areas, the HTLV-1 prevalence in the adult population ranges from 0.3 to 3%, increases with age, and is highest among women. In rural areas of Gabon and the Democratic Republic of the Congo (DRC), HTLV-1 prevalence can reach up to 10-25% in elder women. HTLV-1-associated diseases in African patients have rarely been reported in situ on hospital wards, by local physicians. With the exception of the Republic of South Africa, DRC and Senegal, most reports on ATL and HAM/TSP in African patients have been published by European and American clinicians and involve immigrants or medical returnees to Europe (France and the UK) and the United States. There is clearly a huge underreporting of these diseases on the African continent. The genetic diversity of HTLV-1 is greatest in Africa, where six distinct genotypes (a, b, d, e, f, g) have been identified. The most frequent genotype in central Africa is genotype b. The other genotypes found in central Africa (d, e, f and g) are very rare. The vast majority of HTLV-1 strains from West and North Africa belong to genotype a, the so-called ‘Cosmopolitan’ genotype. These strains form five clades roughly reflecting the geographic origin of the infected individuals. We have recently shown that some of these clades are the result of recombination between a-WA and a-NA strains. Almost all sequences from southern Africa belong to Transcontinental a-genotype subgroup.
Published: 2023

14. High Human T-Cell Leukemia Virus Type 1c Proviral Loads Are Associated With Diabetes and Chronic Kidney Disease: Results of a Cross-Sectional Community Survey in Central Australia

Author: Mohammad Radwanur Talukder, Richard Woodman, Hai Pham, Kim Wilson, Antoine Gessain, John Kaldor, Lloyd Einsiedel, Alice Springs Hospital, Flinders University [Adelaide, Australia], National Serology Reference Laboratory, 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), University of New South Wales [Sydney] (UNSW), and This study was funded by the National Health and Medical Research Council (project grant 1088517).
Subjects: Microbiology (medical), MESH: Humans, MESH: Human T-lymphotropic virus 1, MESH: Diabetes Mellitus, diabetes, [SDV]Life Sciences [q-bio], MESH: Renal Insufficiency, Chronic, Australia, HTLV-1 proviral load, MESH: Australia, MESH: Adult, MESH: Proviruses, Infectious Diseases, MESH: Cross-Sectional Studies, HTLV-1, MESH: HTLV-I Infections, MESH: Surveys and Questionnaires, MESH: Viral Load, chronic kidney disease, MESH: Leukemia, T-Cell
Abstract: Background A link between chronic inflammation and several noncommunicable diseases (NCDs) has been established. Although chronic infection with the human T-cell leukemia virus type 1 (HTLV-1) is the recognized cause of several inflammatory diseases and these are associated with a high number of HTLV-1–infected cells in peripheral blood (proviral load [PVL]), possible interactions between PVL and NCDs have not been studied at a community level. Methods Adult Aboriginal residents of 7 remote communities were invited to complete a health survey between 25 August 2014 and 30 June 2018. Blood was drawn for HTLV-1 serology and PVL, and relevant medical conditions were obtained from health records. Associations between HTLV-1 PVL and diabetes, chronic kidney disease (CKD), and coronary artery disease (CAD) were determined using logistic regression, adjusting for available confounders. Results Among 510 participants (56% of the estimated adult resident population, 922), 197 (38.6%) were HTLV-1–infected. A high HTLV-1 PVL was associated with a 2-fold increase in the odds of diabetes and CKD (diabetes, adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.06–3.61; P = .033 and CKD: aOR, 2.00; 95% CI, 1.03–3.8; P = .041). A nonsignificant association between high PVL and CAD (aOR, 7.08; 95% CI, 1.00–50.18; P = .05) was found for participants aged Conclusions In a community-based study in central Australia, people with HTLV-1 who had high HTLV-1 PVL were more likely to have diabetes and CKD. These findings have potential clinical implications.
Published: 2023

15. Cocirculation of Two env Molecular Variants, of Possible Recombinant Origin, in Gorilla and Chimpanzee Simian Foamy Virus Strains from Central Africa

Author: Réjane Rua, Mirdad Kazanji, Edouard Betsem, Eric M. Leroy, Augustin Mouinga-Ondémé, Léa Richard, Florence Buseyne, Richard Njouom, Philippe V. Afonso, Antoine Gessain, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7) - PRES Sorbonne Paris Cité, Faculty of Medicine and Biomedical Sciences, University of Yaounde I, Unité de Rétrovirologie, Centre International de Recherches Médicales de Franceville, Unité des Maladies Virales Emergentes [Franceville], Centre Pasteur du Cameroun, Centre Pasteur du Cameroun - Réseau International des Instituts Pasteur, L.R. was personally supported by the Bourse de l'Ecole Normale Supérieure, Faculté Paris Diderot. E.B. was supported by the Virus Cancer Prevention Association and by the Institut National pour le Cancer. This work was supported by the Institut Pasteur in Paris, France, by Programme Transversal de Recherche 437 from the Institut Pasteur, and by the French government program Investissement d'Avenir (grant ANR-10-LABX-62-IBEID)., ANR-10-LABX-0062/10-LABX-0062, IBEID, Integrative Biology of Emerging Infectious Diseases(2010), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Cellule Pasteur UPMC, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris], University of Yaoundé [Cameroun], Centre International de Recherches Médicales de Franceville (CIRMF), Réseau International des Instituts Pasteur (RIIP), This work was supported by the Institut Pasteur in Paris, France, by Programme Transversal de Recherche 437 from the Institut Pasteur, and by the French government program Investissement d’Avenir (grant ANR-10-LABX-62-IBEID), ANR-10-LABX-0062/10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: foamy virus, viruses, Gorilla, Simian foamy virus, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, law.invention, Retrovirus, law, enveloppe protein, Cameroon, Phylogeny, Genetics, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Recombination, Genetic, 0303 health sciences, biology, Phylogenetic tree, [SDV.BA]Life Sciences [q-bio]/Animal biology, virus diseases, Foamy viruses, 3. Good health, Ape Diseases, Molecular epidemiology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Recombinant DNA, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pan troglodytes, Immunology, Microbiology, 03 medical and health sciences, Recombination genetic genetics, Phylogenetics, Virology, biology.animal, Animals, Humans, Gabon, Gene, 030304 developmental biology, Gorilla gorilla, 030306 microbiology, Gene Products, env, biology.organism_classification, Genetic Diversity and Evolution, Insect Science, Retroviridae Infections
Abstract: Simian foamy virus (SFV) is a ubiquitous retrovirus in nonhuman primates (NHPs) that can be transmitted to humans, mostly through severe bites. In the past few years, our laboratory has identified more than 50 hunters from central Africa infected with zoonotic SFVs. Analysis of the complete sequences of five SFVs obtained from these individuals revealed that env was the most variable gene. Furthermore, recombinant SFV strains, some of which involve sequences in the env gene, were recently identified. Here, we investigated the variability of the env genes of zoonotic SFV strains and searched for possible recombinants. We sequenced the complete env gene or its surface glycoprotein region (SU) from DNA amplified from the blood of (i) a series of 40 individuals from Cameroon or Gabon infected with a gorilla or chimpanzee foamy virus (FV) strain and (ii) 1 gorilla and 3 infected chimpanzees living in the same areas as these hunters. Phylogenetic analyses revealed the existence of two env variants among both the gorilla and chimpanzee FV strains that were present in zoonotic and NHP strains. These variants differ greatly (>30% variability) in a 753-bp-long region located in the receptor-binding domain of SU, whereas the rest of the gene is very conserved. Although the organizations of the Env protein sequences are similar, the potential glycosylation patterns differ between variants. Analysis of recombination suggests that the variants emerged through recombination between different strains, although all parental strains could not be identified. IMPORTANCE SFV infection in humans is a great example of a zoonotic retroviral infection that has not spread among human populations, in contrast to human immunodeficiency viruses (HIVs) and human T-lymphotropic viruses (HTLVs). Recombination was a major mechanism leading to the emergence of HIV. Here, we show that two SFV molecular envelope gene variants circulate among ape populations in Central Africa and that both can be transmitted to humans. These variants differ greatly in the SU region that corresponds to the part of the Env protein in contact with the environment. These variants may have emerged through recombination between SFV strains infecting different NHP species.
Published: 2015

16. Adult T-Cell Leukemia/Lymphoma in a Caucasian Patient After Sexual Transmission of Human T-Cell Lymphotropic Virus Type 1

Author: Christophe Pasquier, Isabelle Duga, Ali Bazarbachi, Chantal Brouzes, Alexandra Desrames, Olivier Cassar, Franck Mortreux, Claire Sibon, Antoine Gessain, Eric Wattel, David Sibon, David Ghez, Olivier Hermine, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Laboratoire d'hématologie ( ERL 8254 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Hématologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Hôpital Ambroise Paré, Oncovirologie et Biothérapies, Centre National de la Recherche Scientifique ( CNRS ), American University of Beirut [Beyrouth], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital Ambroise Paré [AP-HP], Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), American University of Beirut [Beyrouth] (AUB), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Ziani, Isma, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Sexual transmission, viruses, viral genotyping, lymphoma, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ATLL, Virus, Adult T-cell leukemia/lymphoma, 03 medical and health sciences, 0302 clinical medicine, HTLV-1 transmission, immune system diseases, hemic and lymphatic diseases, Medicine, Human T cell lymphotropic virus type 1, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, 0303 health sciences, biology, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, business.industry, virus diseases, medicine.disease, biology.organism_classification, Virology, 3. Good health, Lymphoma, Leukemia, Infectious Diseases, Oncology, HTLV-1, 030220 oncology & carcinogenesis, Human T-lymphotropic virus 1, Immunology, Brief Reports, business, Breast feeding
Abstract: Adult T-cell leukemia/lymphoma (ATLL), a T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1), develops in the majority of cases in individuals who were infected with HTLV-1 as young children, by their mother during prolonged breastfeeding. We report the case of a Caucasian French man, whose parents were HTLV-1-seronegative and who developed ATLL after HTLV-1 sexual transmission by a Cameroonian woman. This hypothesis was corroborated by genotyping of the patient's virus, which revealed an HTLV-1B strain, found only in Central Africa, especially in Cameroon. Thus, ATLL may develop after HTLV-1 infection during adulthood, outside breastfeeding.
Published: 2015

17. Gag-Specific CD4 and CD8 T-Cell Proliferation in Adolescents and Young Adults with Perinatally Acquired HIV-1 Infection Is Associated with Ethnicity — The ANRS-EP38- IMMIP Study Specific CD4 and CD8 T-Cell Proliferation in Adolescents and Young Adults with Perinatally Acquired HIV-1 Infection Is Associated with Ethnicity

Author: Le Chenadec, Jérôme, Scott-Algara, Daniel, Blanche, Stéphane, Didier, Céline, Montange, Thomas, Viard, Jean-Paul, Dollfus, Catherine, Avettand-Fenoel, Véronique, Rouzioux, Christine, Warszawski, Josiane, Buseyne, Florence, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulation des Infections Rétrovirales, Institut Pasteur [Paris] (IP), 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), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Virologie [CHU Necker], This work was supported by the 2006-232 and 2009-165 grants from 'Agence Nationale de recherche sur le SIDA et les Hépatites' (ANRS, www.anrs.fr) and by 'Fondation AREVA' (http://www.areva.com/FR/groupe-910/fondation-implication-societale-pour-un-developpement-durable.html)., ANRS-EP38-IMMIP, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'Hématologie et Oncologie pédiatriques, Hôpital Trousseau [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) ( EA 7327 ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, CD8 T lymphocytes, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, HIV, ethnicity, [ SDV.IMM.IA ] Life Sciences [q-bio]/Immunology/Adaptive immunology, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, perinatal HIV
Abstract: International audience; The ANRS-EP38-IMMIP study aimed to provide a detailed assessment of the immune status of perinatally infected youths living in France. We studied Gag-specific CD4 and CD8 T-cell proliferation and the association between the proliferation of these cells, demographic factors and HIV disease history. We included 93 youths aged between 15 and 24 years who had been perinatally infected with HIV. Sixty-nine had undergone valid CFSE-based T-cell proliferation assays. Gag-specific proliferation of CD4 and CD8 T cells was detected in 12 (16%) and 30 (38%) patients, respectively. The Gag-specific proliferation of CD4 and CD8 T cells was more frequently observed in black patients than in patients from other ethnic groups (CD4: 32% vs. 4%, P = 0.001; CD8: 55% vs. 26%, P = 0.02). Among aviremic patients, the duration of viral suppression was shorter in CD8 responders than in CD8 nonresponders (medians: 54 vs. 20 months, P = 0.04). Among viremic patients, CD8 responders had significantly lower plasma HIV RNA levels than CD8 nonresponders (2.7 vs. 3.7 log 10 HIV-RNA copies/ml, P = 0.02). In multivariate analyses including sex and HIV-1 subtype as covariables, Gag-specific CD4 T-cell proliferation was associated only with ethnicity, whereas Gag-specific CD8 T-cell proliferation was associated with both ethnicity and the duration of viral suppression. Both CD4 and CD8 responders reached their nadir CD4 T-cell percentages at younger ages than their nonresponder counterparts (6 vs. 8 years, P = 0.04 for both CD4 and CD8 T-cell proliferation). However, these associations were not significant in multivariate analysis. In conclusion, after at least 15 years of HIV infection, Gag-specific T-cell proliferation PLOS ONE
Published: 2015

18. Resequencing Microarray Technology for Genotyping Human Papillomavirus in Cervical Smears

Author: Nicolas Berthet, Claudia Filippone, Isabelle Heard, Michel Favre, Christine Bole-Feysot, Michaël Falguières, Sylvain Brisse, Antoine Gessain, Chloé Bertolus, Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence pour les Papillomavirus Humains - Génétique, Papillomavirus et Cancer Humain (CNR-HPV), Institut Pasteur [Paris], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génotypage des Pathogènes et Santé Publique (Plate-forme) (PF8), Université Pierre et Marie Curie - Paris 6 (UPMC), Génétique, Papillomavirus et Cancer Humain, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre National de Référence pour les Papillomavirus Humains - Génétique, Papillomavirus et Cancer Humain ( CNR-HPV ), Centre d'Immunologie et de Maladies Infectieuses ( CIMI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Chirurgie Maxillo-faciale et stomatologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Génotypage des Pathogènes et Santé Publique (Plate-forme) ( PF8 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and HAL UPMC, Gestionnaire
Subjects: Viral Diseases, Microarray, Microarrays, Gynecologic Infections, lcsh:Medicine, Alphapapillomavirus, 0302 clinical medicine, Genotype, Medicine and Health Sciences, Cluster Analysis, lcsh:Science, Phylogeny, Oligonucleotide Array Sequence Analysis, Genetics, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, Obstetrics and Gynecology, Cervical smears, 3. Good health, Real-time polymerase chain reaction, Infectious Diseases, Bioassays and Physiological Analysis, Medical Microbiology, 030220 oncology & carcinogenesis, Female, Research Article, Human Papillomavirus Infection, food.ingredient, Molecular Sequence Data, Sexually Transmitted Diseases, Biology, Research and Analysis Methods, Real-Time Polymerase Chain Reaction, Microbiology, 03 medical and health sciences, food, Virology, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Humans, Clinical significance, Genotyping, 030304 developmental biology, DNA Primers, Vaginal Smears, Base Sequence, lcsh:R, Biology and Life Sciences, Computational Biology, Sequence Analysis, DNA, Viral Classification, DNA, Viral, Gene chip analysis, Women's Health, lcsh:Q, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; There are more than 40 human papillomaviruses (HPVs) belonging to the alpha genus that cause sexually transmitted infections; these infections are among the most frequent and can lead to condylomas and anogenital intra-epithelial neoplasia. At least 18 of these viruses are causative agents of anogenital carcinomas. We evaluated the performance of a resequencing microarray for the detection and genotyping of alpha HPV of clinical significance using cloned HPV DNA. To reduce the number of HPV genotypes tiled on microarray, we used reconstructed ancestral sequences (RASs) as they are more closely related to the various genotypes than the current genotypes are among themselves. The performance of this approach was tested by genotyping with a set of 40 cervical smears already genotyped using the commercial PapilloCheck kit. The results of the two tests were concordant for 70% (28/40) of the samples and compatible for 30% (12/40). Our findings indicate that RASs were able to detect and identify one or several HPV in clinical samples. Associating RASs with homonym sequences improved the genotyping of HPV present in cases of multiple infection. In conclusion, we demonstrate the diagnostic potential of resequencing technology for genotyping of HPV, and illustrate its value both for epidemiological studies and for monitoring the distribution of HPV in the post-vaccination era.
Published: 2014

19. Neutralization of zoonotic retroviruses by human antibodies: Genotype-specific epitopes within the receptor-binding domain from simian foamy virus

Author: Lasse Toftdal Dynesen, Ignacio Fernandez, Youna Coquin, Manon Delaplace, Thomas Montange, Richard Njouom, Chanceline Bilonga-Ndongo, Felix A. Rey, Antoine Gessain, Marija Backovic, Florence Buseyne, 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), Virologie Structurale - Structural Virology, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Ministère de la Santé Publique [Yaoundé, Cameroun], This work was supported by the Agence Nationale de la Recherche (ANR-10-LABX62-IBEID, Intra-Labex Grant (MB)), and the Programme de Recherche Transversal from the Institut Pasteur (PTR2020-353 ZOOFOAMENV, FB). SFV protein production was supported by the European Virus Archive-GLOBAL project, which has received funding from the EU Horizon 2020 Research and Innovation Programme (grant agreement number 871029). LTD was supported by the Pasteur-Paris-University (PPU) International Doctoral Program and the Fondation pour la Recherche Médicale, including additional supportive funding from the Danish Pasteur Society, Augustinus Fonden, Knud-Højgaards Fond, and Viet-Jacobsen Fonden., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and European Project: 871029,H2020,H2020-INFRAIA-2019-1,EVA-GLOBAL(2020)
Subjects: [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Virology, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, Parasitology, Molecular Biology, Microbiology
Abstract: Infection with viruses of animal origin pose a significant threat to human populations. Simian foamy viruses (SFVs) are frequently transmitted to humans, in which they establish a life-long infection, with the persistence of replication-competent virus. However, zoonotic SFVs do not induce severe disease nor are they transmitted between humans. Thus, SFVs represent a model of zoonotic retroviruses that lead to a chronic infection successfully controlled by the human immune system. We previously showed that infected humans develop potent neutralizing antibodies (nAbs). Within the viral envelope (Env), the surface protein (SU) carries a variable region that defines two genotypes, overlaps with the receptor binding domain (RBD), and is the exclusive target of nAbs. However, its antigenic determinants are not understood. Here, we characterized nAbs present in plasma samples from SFV-infected individuals living in Central Africa. Neutralization assays were carried out in the presence of recombinant SU that compete with SU at the surface of viral vector particles. We defined the regions targeted by the nAbs using mutant SU proteins modified at the glycosylation sites, RBD functional subregions, and genotype-specific sequences that present properties of B-cell epitopes. We observed that nAbs target conformational epitopes. We identified three major epitopic regions: the loops at the apex of the RBD, which likely mediate interactions between Env protomers to form Env trimers, a loop located in the vicinity of the heparan binding site, and a region proximal to the highly conserved glycosylation site N8. We provide information on how nAbs specific for each of the two viral genotypes target different epitopes. Two common immune escape mechanisms, sequence variation and glycan shielding, were not observed. We propose a model according to which the neutralization mechanisms rely on the nAbs to block the Env conformational change and/or interfere with binding to susceptible cells. As the SFV RBD is structurally different from known retroviral RBDs, our data provide fundamental knowledge on the structural basis for the inhibition of viruses by nAbs. Trial registration: The study was registered at www.clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT03225794/.
Published: 2023

20. Transmission des arbovirus par allaitement : le virus Zika et le virus de la fièvre jaune

Author: Desgraupes, Sophie, 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), Université Paris Cité, and Pierre-Emmanuel Ceccaldi
Subjects: transmission mère-enfant, allaitement, Virus Zika, breastfeeding, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, mother-to-child transmission, virus de la fièvre jaune, epithelial crossing, franchissement d’épithélium, antiviral, Zika virus, yellow fever virus
Abstract: The transmission of certain arboviruses (“arthropod-borne viruses”) by breastfeeding has been suggested in humans (e.g. Zika virus (ZIKV), yellow fever virus (YFV), Dengue virus, West Nile virus...). Among these, ZIKV and YFV are particularly discussed. For ZIKV, numerous case reports show the presence of the virus in breast milk and the infection of the breastfed infant, while for YFV, viral transmission through breastfeeding has been observed for the vaccine strain (not transmitted by mosquitoes). It is necessary to understand the importance of breastfeeding in the transmission of these arboviruses to prevent their transmission to newborns through breastfeeding during future outbreaks. In our laboratory, we have previously demonstrated the transmission of ZIKV by breastfeeding in the A129 mouse model (IFNAR KO). We also demonstrated that ZIKV disseminates to the mammary glands and infects mammary epithelial cells (using the mouse model, primary human mammary epithelial cells and cell lines). Finally, we showed that ZIKV crosses the intestinal barrier in vivo and in vitro, and we identified the mechanism of crossing as being the productive infection of the epithelium without alteration of its barrier function. However, some case studies have reported a lack of transmission of ZIKV to breastfed newborns by an infected mother. Different biological or genetic factors controlling the transmission of other viruses by breastfeeding (i.e. human immunodeficiency virus, human T- lymphotropic virus, cytomegalovirus) have been described: viral load and infectious viral form in breast milk, immunological status of the mother, duration of breastfeeding, etc. In this doctoral project, we studied the infectious form of ZIKV in murine breast milk and detected free and cell-associated virus. We also studied the effect of milk components on ZIKV infection and observed an inhibitory effect of long chain fatty acids. In a second axis, we studied the mechanisms of YFV transmission to newborns during breastfeeding, using in vitro and in vivo models (A129 mice). We studied the vaccine strain 17D-204 (transmitted by breastfeeding in humans) as well as two wild type strains (Asibi and Dakar) to assess whether the latter could also be transmitted by breastfeeding. We showed that YFV disseminates to murine mammary glands after infection and that free infectious viral particles are excreted in breast milk. In vitro, we have shown that human mammary epithelial cell lines are permissive to infection, and we have suggested a mechanism of intestinal barrier crossing of the newborn. Like ZIKV, the three YFV strains tested cross the intestinal barrier by productive infection of the epithelium without altering its barrier function. In conclusion, this doctoral project has allowed us to demonstrate the presence of ZIKV in murine breast milk both in a free and "cell-associated" form, to identify an inhibitory effect of certain free fatty acids in milk on ZIKV, and to address the mechanisms of transepithelial passage of YFV at the mammary and intestinal barriers. These results provide elements of understanding in the evaluation, or even prevention, of the risk of transmission of these two viruses by breastfeeding.; La transmission de certains arbovirus (« arthropode-borne virus ») par allaitement a été suggérée chez l’Homme (e.g. virus Zika (ZIKV), virus de la fièvre jaune (YFV), virus de la Dengue, virus West Nile...). Parmi ceux-ci, ZIKV et YFV sont particulièrement discutés. Pour ZIKV, de nombreuses études de cas rapportent la présence du virus dans le lait maternel et l’infection du nourrisson allaité tandis que pour YFV la transmission virale par allaitement a été observée pour la souche vaccinale, non transmise par les moustiques. Il est nécessaire de comprendre l’importance que représente l’allaitement dans la transmission de ces arbovirus afin de prévenir l’infection des nourrissons par allaitement lors de futures épidémies.Au laboratoire, nous avions précédemment montré la transmission de ZIKV par allaitement sur le modèle murin A129 (IFNAR KO). Nous avions également démontré que ZIKV dissémine aux glandes mammaires et infecte les cellules épithéliales mammaires (à l’aide du modèle murin, de cellules épithéliales mammaires humaines primaires et de lignées cellulaires). Enfin nous avions montré que ZIKV franchit la barrière intestinale in vivo et in vitro et nous avions proposé un mécanisme de franchissement comme étant l’infection productive de l’épithélium sans altération de sa fonction de barrière.Cependant, certaines études de cas ont rapporté une absence de transmission de ZIKV à des nourrissons allaités par une mère infectée. Différents facteurs biologiques ou génétiques contrôlant la transmission d’autres virus par allaitement (i.e. virus de l’immunodéficience humaine, virus T-lymphotrope humain, cytomégalovirus) ont été décrits : la charge virale et la forme virale infectieuse dans le lait, le statut immunologique de la mère, la durée de l’allaitement, etc. Dans ce projet doctoral, nous avons étudié la forme infectieuse de ZIKV dans le lait maternel murin et nous avons détecté du virus libre et « cellule-associé ». Nous avons également étudié l’effet des composants du lait sur l’infection par ZIKV et nous avons observé un effet inhibiteur des acides gras à longue chaîne carbonée.Dans un second axe, nous avons étudié les mécanismes de transmission de YFV par allaitement au nourrisson à l’aide de modèles in vitro et in vivo (souris A129). Nous avons étudié la souche vaccinale 17D-204 (transmise par allaitement chez l’Homme) ainsi que 2 souches sauvages (Asibi et Dakar) afin d’évaluer si ces dernières pourraient également être transmises par allaitement. Nous avons montré que YFV dissémine aux glandes mammaires murines après l’infection et que des particules infectieuses sont excrétées dans le lait. In vitro, nous avons montré que des lignées épithéliales mammaires humaines sont permissives à l’infection et nous avons proposé un mécanisme de franchissement de la barrière intestinale du nourrisson. À l’instar de ZIKV, les 3 souches de YFV testées franchissent la barrière intestinale par infection productive de l’épithélium sans altération de sa fonction de barrière.En conclusion, ce projet doctoral a permis de mettre en évidence la présence de ZIKV dans le lait maternel murin sous forme libre et « cellule-associée », d’identifier un effet inhibiteur de certains acides gras libres du lait sur ZIKV, ainsi que d’aborder les mécanismes de passage transépithélial de YFV au niveau des barrières mammaire et intestinale. Ces résultats apportent des éléments de compréhension dans l’évaluation, voire la prévention, du risque de transmission de ces deux virus par allaitement.
Published: 2022

21. L'infection humaine par les virus foamy simiens zoonotiques : caractérisation des épitopes reconnus par les anticorps neutralisants chez l’homme infecté

Author: Dynesen, Lasse Toftdal, 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), Programme Transversal de Recherche from the Institut Pasteur PTR2020-353 ZOOFOAMENV, Pasteur-Paris University (PPU) International Doctoral Program, Fondation pour la Recherche Médicale, Université Paris Cité, and Florence Buseyne
Subjects: retrovirus, zoonose, epitope, Simian foamy virus, épitope, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, neutralizaing antibodies, zoonosis, Virus foamy simiens, anticorps neutralisant
Abstract: Simian foamy viruses (SFVs) are ancient and wide-spread complex-type retroviruses that have co-evolved with their non-human primate (NHP) species for millions of years. These viruses can be transmitted to humans, primarily through bites, leading to the establishment of a life-long persistent infection. Despite frequent zoonotic transmission of SFVs from NHPs to humans in Central Africa and Asia, no overt pathology or human-to-human transmission of SFVs have been reported yet. My host laboratory hypothesized that the immune system efficiently controls viral replication in zoonotically infected humans. They demonstrated that neutralizing antibodies (nAbs) are present at high titers in Central African hunters infected with gorilla and chimpanzee SFV strains. My colleagues showed that two viral genotypes are circulating among SFV-infected NHPs and humans. A variant region within the surface domain (SU) of the viral envelope glycoprotein (Env), termed SUvar, forms basis of the two genotypes. The receptor binding domain (RBD) overlaps the SUvar region. The nAbs strictly target the SUvar region on the SFV Env.I aimed to characterize nAb epitopes located within the SUvar region of SFV Env. To map nAb epitopes within SUvar, I performed neutralization assays in presence of recombinant SU proteins that compete with Env at the surface of viral particles for nAb binding. I used plasma samples from Central African hunters infected with gorilla SFVs and foamy viral vectors expressing SFV Env from each of the two genotypes. I generated mutant SU proteins by systematically deleting glycosylation sites, inserting glycans to disrupt epitopes and by swapping residues between the two genotypes.I have described that nAb epitopes have a genotype-specific location. Through collaborative work with the laboratory of Prof. Félix Rey who solved the crystal structure of a gorilla SFV RBD, I have discovered that most SFV-specific nAbs target epitopes located at the apex of Env, in particular three mobile loops located at the interface between protomers. Vectors with deleted loops were produced and bound to cells but were non-infectious, suggesting that nAbs target epitopes with functional importance. In addition, we found a second major epitope in the bottom part of the RBD targeted by nAbs from individuals infected by one of the two genotypes. This region is involved in binding to cells. My results suggest that SFV-specific nAbs could block viral entry either by preventing Env binding to the cell surface or by preventing conformational changes of the Env trimer and fusion of viral and cellular membranes. Collectively, my data support the role of nAbs in the control of viral replication and human-to-human transmission.; Les virus foamy simiens (VFS) sont des rétrovirus de type complexe anciens et très répandus. Ils ont évolué conjointement avec leur espèce hôte pendant des millions d'années. Ces virus peuvent être transmis à l'homme, principalement par des morsures, entraînant l'établissement d'une infection persistante. Malgré la transmission zoonotique fréquente des VFS des PNH aux humains en Afrique centrale et en Asie, aucune pathologie sévère ou transmission interhumaine des VFS n'a encore été décrite. Mon laboratoire a émis l'hypothèse que le système immunitaire contrôle efficacement la réplication virale chez les humains infectés par des zoonoses. Mes collègues ont démontré que des anticorps neutralisants (AcNs) sont présents à des titres élevés chez les chasseurs d'Afrique centrale infectés par des souches de VFS de gorille et de chimpanzé. Deux génotypes viraux circulent parmi les primates non humains (PNHs) et les hommes infectés par le VFS. Une région variante au sein du domaine de surface (SU) de la glycoprotéine d'enveloppe virale (Env), appelée SUvar, constitue la base des deux génotypes. Le domaine de liaison au récepteur (RBD, pour receptor binding domain) chevauche la région SUvar. Ces anticorps neutralisants ciblent strictement la région SUvar de l'Env du VFS.Mon objectif était de caractériser les épitopes reconnus par les AcN situés dans la région SUvar de l'Env du VFS. Pour cartographier les épitopes AcN au sein de la SUvar, j'ai réalisé des tests de neutralisation en présence de protéines SU recombinantes agissant comme compétiteurs de l’enveloppe des particules virales pour la liaison aux AcN. J'ai utilisé des échantillons de plasma provenant de chasseurs d'Afrique centrale infectés par le VFS du gorille et des vecteurs viraux foamy exprimant l'Env du VFS de l'un ou l'autre des deux génotypes. J'ai généré des protéines SU mutantes en supprimant systématiquement des sites de glycosylation, en insérant des sites de glycosylation pour modifier des épitopes et en échangeant des domaines entre les deux génotypes.J'ai montré que les épitopes neutralisants ont une localisation spécifique au génotype. Grâce à une collaboration avec le laboratoire du professeur Félix Rey qui a résolu une structure d'un RBD du VFS du gorille, j’ai pu montré que la plupart des AcNs spécifiques du VFS ciblent des épitopes situés à l'apex de Env, en particulier trois boucles mobiles situées à l'interface entre les protomères. Des vecteurs dont l’enveloppe est délétée pour chacune de ces boucles se fixent aux cellules mais sont non infectieux, ce qui suggère que les AcNs ciblent des épitopes ayant une importance fonctionnelle. De plus, nous avons trouvé un deuxième épitope majeur dans la partie inférieure du RBD ciblé par les AcNs provenant d'individus infectés par l'un des deux génotypes. Cette région est impliquée dans la fixation aux cellules. Mes résultats suggèrent que les AcNs spécifiques du VFS pourraient bloquer l'entrée du virus, soit en inhibant l’interaction entre Env et la surface de la cellule soit en empêchant le changement de conformation de Env permettant la fusion des membranes virale et cellulaire. Mes données confirment que les AcNs pourraient contribuer à contrôler la réplication virale et la transmission interhumaine des VFS.
Published: 2022

22. Des peptides dérivés de claudines inhibent les infections à Flavivirus

Author: Zoladek, Jim, Afonso, Philippe V., Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: [SDV]Life Sciences [q-bio], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Abstract: International audience; No abstract available
Published: 2022

23. The genomic landscape of contemporary western Remote Oceanians

Author: Lara R. Arauna, Jacob Bergstedt, Jeremy Choin, Javier Mendoza-Revilla, Christine Harmant, Maguelonne Roux, Alex Mas-Sandoval, Laure Lémée, Heidi Colleran, Alexandre François, Frédérique Valentin, Olivier Cassar, Antoine Gessain, Lluis Quintana-Murci, Etienne Patin, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Karolinska Institutet [Stockholm], Collège de France (CdF (institution)), Universidad Peruana Cayetano Heredia (UPCH), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Université Paris Cité (UPCité), Imperial College London, Institut Pasteur [Paris], Biomics (plateforme technologique), Max Planck Institute for Evolutionary Anthropology [Leipzig], Max-Planck-Gesellschaft, Lattice - Langues, Textes, Traitements informatiques, Cognition - UMR 8094 (Lattice), Université Sorbonne Nouvelle - Paris 3-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris sciences et lettres (PSL)-Département Littératures et langage - ENS Paris (LILA), 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), Technologie et Ethnologie des Mondes Préhistoriques (TEMPS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), L.R.A. was funded by a Pasteur-Roux-Cantarini fellowship from 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 programme, 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 (Equipe FRM DEQ20180339214), and the French National Research Agency (ANR-19-CE35-0005)., 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), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), and Institut Pasteur [Paris] (IP)
Subjects: Native Hawaiian or Other Pacific Islander, diversification, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, peopling, Human Migration, Remote Oceania, Papuans, General Biochemistry, Genetics and Molecular Biology, Pacific migrations, Vanuatu, Lapita, Humans, genetics, DNA, Ancient, ancient DNA, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Genome, Human, migrations, language contact, Genomics, residence rules, Pacific, Genetics, Population, Melanesians, assortative mating, admixture, General Agricultural and Biological Sciences, Polynesian outliers
Abstract: SUMMARYThe Vanuatu archipelago served as a gateway to Remote Oceania during one of the most extensive human migrations to uninhabited lands, ~3,000 years ago. Ancient DNA studies suggest an initial settlement by East Asian-related peoples that was quickly followed by the arrival of Papuan-related populations, leading to a major population turnover. Yet, there is uncertainty over the population processes and the sociocultural factors that have shaped the genomic diversity of ni-Vanuatu, who present nowadays among the world’s highest linguistic and cultural diversity. Here, we report new genome-wide data for 1,433 contemporary ni-Vanuatu from 29 different islands, including 287 couples. We find that ni-Vanuatu derive their East Asian- and Papuan-related ancestry from the same source populations and descend from relatively synchronous, sex-biased admixture events that occurred ~1,700-2,300 years ago, indicating a peopling history common to all the archipelago. However, East Asian-related ancestry proportions differ markedly across islands, suggesting that the Papuan-related population turnover was geographically uneven. Furthermore, we detect Polynesian ancestry arriving ~600-1,000 years ago to South Vanuatu in both Polynesian- and non-Polynesian-speaking populations. Lastly, we provide evidence for a tendency of spouses to carry similar genetic ancestry, when accounting for relatedness avoidance. The signal is not driven by strong genetic effects of specific loci or trait-associated variants, suggesting that it results instead from social assortative mating. Altogether, our findings provide insight into both the genetic history of ni-Vanuatu populations and how sociocultural processes have shaped the diversity of their genomes.
Published: 2022

24. Monkeypox

Author: Antoine Gessain, Emmanuel Nakoune, Yazdan Yazdanpanah, 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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), and Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS)
Subjects: MESH: Monkeypox, MESH: Humans, [SDV]Life Sciences [q-bio], General Medicine, Monkeypox, Disease Outbreaks, MESH: Monkeypox virus, Zoonoses, Animals, Humans, MESH: Animals, MESH: Disease Outbreaks, Monkeypox virus, MESH: Zoonoses
Abstract: International audience; No abstract available
Published: 2022

25. Human Claudin-Derived Peptides Block the Membrane Fusion Process of Zika Virus and Are Broad Flavivirus Inhibitors

Author: Jim Zoladek, Julien Burlaud-Gaillard, Maxime Chazal, Sophie Desgraupes, Patricia Jeannin, Antoine Gessain, Nathalie Pardigon, Mathieu Hubert, Philippe Roingeard, Nolwenn Jouvenet, Philippe V. Afonso, Institut Pasteur [Paris] (IP), Université Paris Cité (UPCité), 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), Université de Tours (UT), 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), Virologie (CNRS - UMR3569), Signalisation antivirale - Virus sensing and signaling, Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity, 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). Jim Zoladek and Sophie Desgraupes were the recipients of Ph.D. fellowships from the ED562-BioSPC and the French ministry of education and research., We thank Nicoletta Casartelli for her help on HIV-1-related experiments. We thank Florence Guivel-Benhassine for help with virus titration, Charlotte Calvet for help with sample preparation for scanning electron microscopy, Sylvie Van der Werf for the SARS-CoV-2 isolate used in this study, and Nicolas Escriou for the gift of a SARS-CoV-2 spike antibody. We thank Stéphane Roche for his biochemistry-related input and discussions on the project. We thank Pierre-Emmanuel Ceccaldi for his input and discussions on the project., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Afonso, Philippe, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Virologie (CNRS-UMR3569), and Virus et Immunité - Virus and immunity (CNRS-UMR3569)
Subjects: Microbiology (medical), [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, General Immunology and Microbiology, Ecology, Physiology, Zika Virus Infection, flavivirus, Cell Biology, Zika Virus, Antiviral Agents, Lipids, Membrane Fusion, antimicrobial peptides, Infectious Diseases, Zika, Claudin-1, Claudins, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, claudin, Humans, Peptides
Abstract: International audience; Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged in the Pacific islands in 2007 and spread to the Americas in 2015. The infection remains asymptomatic in most cases but can be associated with severe neurological disorders. Despite massive efforts, no specific drug or vaccine against ZIKV infection is available to date. Claudins are tight-junction proteins that favor the entry of several flaviviruses, including ZIKV. In this study, we identified two peptides derived from the N-terminal sequences of claudin-7 and claudin-1, named CL7.1 and CL1.1, respectively, that inhibited ZIKV infection in a panel of human cell lines. Using cell-to-cell fusion assays, we demonstrated that these peptides blocked the ZIKV E-mediated membrane fusion. A comparison of the antiviral efficacy of CL1.1 and CL7.1 pointed to the importance of the peptide amphipathicity. Electron microscopic analysis revealed that CL1.1 altered the ultrastructure of the viral particles likely by binding the virus lipid envelope. However, amphipathicity could not fully explain the antiviral activity of CL1.1. In silico docking simulations suggested that CL1.1 may also interact with the E protein, near its stem region. Overall, our data suggested that claudin-derived peptides inhibition may be linked to simultaneous interaction with the E protein and the viral lipid envelope. Finally, we found that CL1.1 also blocked infection by yellow fever and Japanese encephalitis viruses but not by HIV-1 or SARS-CoV-2. Our results provide a basis for the future development of therapeutics against a wide range of endemic and emerging flaviviruses. IMPORTANCE Zika virus (ZIKV) is a flavivirus transmitted by mosquito bites that have spread to the Pacific Islands and the Americas over the past decade. The infection remains asymptomatic in most cases but can cause severe neurological disorders. ZIKV is a major public health threat in areas of endemicity, and there is currently no specific antiviral drug or vaccine available. We identified two antiviral peptides deriving from the N-terminal sequences of claudin-7 and claudin-1 with the latter being the most effective. These peptides block the envelope-mediated membrane fusion. Our data suggested that the inhibition was likely achieved by simultaneously interacting with the viral lipid envelope and the E protein. The peptides also inhibited other flaviviruses. These results could provide the basis for the development of therapies that might target a wide array of flaviviruses from current epidemics and possibly future emergences.
Published: 2022

26. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood

Author: Bernhard Fleckenstein, Lazaro Lorenzo, Martin Olivier, Antoine Gessain, Nur Canpolat, Cindy S. Ma, Vincent Pedergnana, Olivier Cassar, Jinjong Myoung, Michael Croft, Avinash Abhyankar, Jean-Laurent Casanova, Monika Schmidt, Emmanuelle Jouanguy, Laurent Abel, Danielle T. Avery, Ethel Cesarman, Stuart G. Tangye, Capucine Picard, Flore Rozenberg, Arzu Akcay, Gonul Aydogan, Philippe Gros, Jacinta Bustamante, Mélanie Migaud, Minji Byun, Yifang Liu, Umaimainthan Palendira, Hye Kyung Lim, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, rockefeller university, Immunology Program, Garvan Institute of medical research, St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales [Sydney] ( UNSW ), Pediatric Hematology and Oncology, Kanuni Sultan Suleyman Education and Research Hospital, Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Novartis Institutes for BioMedical Research, Department of Pathology and Laboratory Medicine, Weil Cornell Medical College, Institut für Klinische und Molekulare Virologie, Friedrich-Alexander Universität Erlangen-Nürnberg ( FAU ), Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université Paris Descartes - Paris 5 ( UPD5 ), Department of Pediatric Nephrology, Cerrahpasa Faculty of Medicine, Istanbul University, CHU Necker - Enfants Malades [AP-HP], McGill University, La Jolla Institute for Allergy & Immunology ( LA JOLLA Institute ), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], The Laboratory of Human Genetics of Infectious Diseases is supported by grants from the Institut National de la Santé et de la Recherche Médicale, University Paris Descartes, the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID), the St. Giles Foundation, the National Center for Research Resources and the National Center for Advancing Sciences (NCATS) grant number 8UL1TR000043 from the National Institutes of Health, and the Rockefeller University. M. Byun is supported by the Charles H. Revson Foundation and formerly by the Irvington Institute Fellowship Program of the Cancer Research Institute. C.S. Ma, U. Palendira, and S.G. Tangye are supported by the National Health and Medical Research Council of Australia and Cancer Council New South Wales. E. Cesarman is funded by National Institutes of Health grants R01CA103646 and R01CA154228. J.-L. Casanova is a member of the Sanofi Strategic Development and Scientific Advisory Committee. The authors have no additional conflicting financial interests., ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' ( 2010 ), Ziani, Isma, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], University of New South Wales [Sydney] (UNSW), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Novartis Institutes for BioMedical Research (NIBR), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), McGill University = Université McGill [Montréal, Canada], La Jolla Institute for Immunology [La Jolla, CA, États-Unis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio], Inheritance Patterns, Intracellular Space, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, T-Lymphocyte Subsets, Immunology and Allergy, IL-2 receptor, Age of Onset, Child, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, 0303 health sciences, Homozygote, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Female, Adult, Cell type, T cell, Molecular Sequence Data, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, Article, Young Adult, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigen, Immunity, medicine, Humans, Amino Acid Sequence, Cysteine, Lymphocyte Count, Sarcoma, Kaposi, 030304 developmental biology, Classic Kaposi Sarcoma, Base Sequence, [ SDV ] Life Sciences [q-bio], Cell Membrane, HEK 293 cells, biochemical phenomena, metabolism, and nutrition, Receptors, OX40, HEK293 Cells, Amino Acid Substitution, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Antibody Formation, Mutation, Mutant Proteins, Immunologic Memory, CD8, 030215 immunology
Abstract: Human OX40 is necessary for robust CD4+ T cell memory and confers selective protective immunity against HHV-8 infection in endothelial cells., Kaposi sarcoma (KS), a human herpes virus 8 (HHV-8; also called KSHV)–induced endothelial tumor, develops only in a small fraction of individuals infected with HHV-8. We hypothesized that inborn errors of immunity to HHV-8 might underlie the exceedingly rare development of classic KS in childhood. We report here autosomal recessive OX40 deficiency in an otherwise healthy adult with childhood-onset classic KS. OX40 is a co-stimulatory receptor expressed on activated T cells. Its ligand, OX40L, is expressed on various cell types, including endothelial cells. We found OX40L was abundantly expressed in KS lesions. The mutant OX40 protein was poorly expressed on the cell surface and failed to bind OX40L, resulting in complete functional OX40 deficiency. The patient had a low proportion of effector memory CD4+ T cells in the peripheral blood, consistent with impaired CD4+ T cell responses to recall antigens in vitro. The proportion of effector memory CD8+ T cells was less diminished. The proportion of circulating memory B cells was low, but the antibody response in vivo was intact, including the response to a vaccine boost. Together, these findings suggest that human OX40 is necessary for robust CD4+ T cell memory and confers apparently selective protective immunity against HHV-8 infection in endothelial cells.
Published: 2013

27. HTLV-1-associated inflammatory myopathies: low proviral load and moderate inflammation in 13 patients from West Indies and West Africa

Author: Marion Desdouits, Thomas Papo, Franck Mortreux, Simona Ozden, Arnaud Lacour, Anne-Sophie Morin, Olivier Hermine, Olivier Gout, Thierry Maisonobe, Eric Wattel, Graham P. Taylor, Sandra Martin-Latil, Michel Huerre, Julien Haroche, Olivier Benveniste, Alexandra Desrames, Antônio Lúcio Teixeira, Marie-Christine Cumont, Antoine Gessain, Serge Herson, Gillian Butler-Browne, Marc Polivka, Fabien Zagnoli, Pascale Marcorelles, Jacqueline Mikol, Isabelle Pénisson-Besnier, Pierre-Emmanuel Ceccaldi, Olivier Cassar, Patrick Cherin, Zahir Amoura, Achille Aouba, Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'épidémiologie sur les causes médicales de décès (CépiDc), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Bichat - Claude Bernard, French Military Hospital Clermont-Tonnerre, Service de Médecine Interne, GH Bichat-Claude Bernard, Paris, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Neuropathologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP], Service d'endocrinologie-métabolisme [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Service de médecine interne [CHU Pitié-Salpétrière], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut E3M [CHU Pitié-Salpêtrière], Service de Médecine interne, Service des maladies neuromusculaires [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Fondation Rothschild, Université Paris Diderot - Paris 7 ( UPD7 ) -PRES Sorbonne Paris Cité, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre d'épidémiologie sur les causes médicales de décès ( CépiDc ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), Université d'Angers ( UA ) -CHU Angers, CHRU Brest - Laboratoire d'Anatomo-Pathologie ( CHU - AnaPath ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre d'Immunologie et de Maladies Infectieuses ( CIMI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Pathology, viruses, Myopathy, [SDV]Life Sciences [q-bio], 0302 clinical medicine, Proviruses, Phylogeny, Myositis, Aged, 80 and over, Human T-lymphotropic virus 1, 0303 health sciences, Middle Aged, Viral Load, 3. Good health, Africa, Western, Leukemia, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, Muscle, Female, Viral disease, Antibody, medicine.symptom, Viral load, Adult, medicine.medical_specialty, West Indies, Inflammation, Biology, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Statistics, Nonparametric, Virus, 03 medical and health sciences, Virology, medicine, Humans, RNA, Messenger, Aged, Retrospective Studies, 030304 developmental biology, [ SDV ] Life Sciences [q-bio], HTLV, medicine.disease, HTLV-I Infections, Immunology, biology.protein, 030217 neurology & neurosurgery
Abstract: Background The Human T-cell Leukemia Virus type 1 (HTLV-1) is the causative agent of several inflammatory diseases, including HTLV-1-associated inflammatory myopathies (HAIM). Little is known about the virological and immunological characteristics of this viral disease. Objectives To characterize the histological and virological features of HAIM patients, in order to better understand the pathogenetic mechanisms and unravel new biological markers of this disease. Study design We conducted a retrospective study on 13 patients with HAIM, based on blood and muscle samples. We included blood samples from HTLV-1-infected individuals without myopathy as controls. Muscle biopsies were used for a broad immunohistological evaluation of tissue damage and inflammation, as well as identification of infected cells through in situ hybridization. DNA extracted from patients’ PBMC was used to identify the virus genotype by sequencing and to assess the proviral load by quantitative PCR. Anti-viral antibodies in plasma samples were titrated by indirect immunofluorescence. Results Patients originate from HTLV-1 endemic areas, the West Indies and West Africa. Histological alterations and inflammation in patients muscles were mostly moderate, with classical features of idiopathic myositis and rare HTLV-1-infected infiltrating cells. In all patients, HTLV-1 belonged to the A subtype, transcontinental subgroup. Anti-HTLV-1 antibodies titers were high, but the proviral load was not elevated compared to asymptomatic HTLV-1 carriers. Conclusion We show here that muscle inflammation is moderate in HAIM, and accompanied by a low HTLV-1 proviral load, suggesting that the pathogenetic events do not exactly mirror those of other HTLV-1-associated inflammatory diseases.
Published: 2013

28. Investigation of a mpox outbreak in Central African Republic, 2021-2022

Author: Besombes, C., Mbrenga, F., Malaka, C., Gonofio, E., Schaeffer, Laura, Konamna, X., Selekon, B., Namsenei-Dankpea, J., Gildas Lemon, C., Landier, J., von Platen, C., Gessain, Antoine, Manuguerra, Jean-Claude, Fontanet, A., Nakouné, E., 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), Sorbonne Université (SU), Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Cellule d'Intervention Biologique d'Urgence (Centre National de Référence) - Laboratory for Urgent Response to Biological Threats (National Reference Center) (CIBU), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), Financial support for this study was provided by the French Agence Nationale de Recherche (ANR 2019CE-35), the PTR (Projets Transversaux de Recherche PTR 218-19) fund from Institut Pasteur Paris, the INCEPTION project (PIA/ANR-16-CONV-005) and the SCOR Foundation for Science., and ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016)
Subjects: Central African Republic, Emerging infectious diseases, mpox, Zoonosis, Surveillance, Infectious Diseases, [SDV]Life Sciences [q-bio], Outbreak investigation, Public Health, Environmental and Occupational Health, Monkeypox virus
Abstract: International audience; Human monkeypox virus is spreading globally, and more information is required about its epidemiological and clinical disease characteristics in endemic countries. We report the investigation of an outbreak in November 2021 in Central African Republic (CAR). The primary case, a hunter, fell ill after contact with a non-human primate at the frontier between forest and savannah. The ensuing investigation in a small nearby town concerned two families and four waves of inter-human transmission, with 14 confirmed cases, 11 suspected cases and 17 non-infected contacts, and a secondary attack rate of 59.5% (25/42). Complications were observed in 12 of the 19 (63.2%) confirmed and suspected cases with available clinical follow-up data: eight cases of bronchopneumonia, two of severe dehydration, one corneal ulcer, one abscess, two cutaneous superinfections, and six cutaneous sequelae (cheloid scars, or depigmentation). There was one death, giving a case fatality ratio of 1/25 (4.0%) for confirmed and suspected cases. This outbreak, with the largest number of confirmed cases ever described in CAR, confirms the potential severity of the disease associated with clade I monkeypox viruses, and highlights the need for rapid control over virus circulation to prevent the further national and international spread of infection.
Published: 2023

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

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

30. Relationships between HIV disease history and blood HIV-1 DNA load in perinatally infected adolescents and young adults: The ANRS-EP38-IMMIP Study

Author: Josiane Warszawski, Véronique Avettand-Fenoel, Stéphane Blanche, Jérôme Le Chenadec, Jean-Paul Viard, Naima Bouallag, Yves Rivière, Florence Buseyne, Daniel Scott-Algara, Christine Rouzioux, Catherine Dollfus, Yassine Benmebarek, Laboratoire de Virologie [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), 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), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], Immunopathologie Virale, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), ANRSFondation AREVA, ANRS-EP38-IMMIP, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hématologie et Oncologie pédiatriques, Hôpital Trousseau [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Université Paris-Sud - Paris 11 ( UP11 ), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) ( EA 7327 ), Epidémiologie et Physiopathologie des Virus Oncogènes, and Buseyne, Florence
Subjects: Male, MESH: CD4 Lymphocyte Count, MESH : Pregnancy Complications, Infectious/virology, HIV Infections, MESH : Viral Load, Disease, law.invention, MESH: Pregnancy Complications, Infectious/virology, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, cell-associated HIV DNA, MESH: HIV Infections/blood, Young adult, HIV perinatal infection, 0303 health sciences, MESH: DNA, Viral/blood, MESH: RNA, Viral/blood, virus diseases, MESH: HIV Infections/transmission, MESH: Follow-Up Studies, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH: Young Adult, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Disease Progression, MESH: Disease Progression, MESH : Viremia, Viral load, MESH : Young Adult, MESH : Cohort Studies, Viremia, MESH : HIV Infections/blood, MESH: HIV-1/isolation & purification, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 03 medical and health sciences, MESH : Adolescent, Humans, MESH : HIV Infections/transmission, MESH: Adolescent, MESH: Humans, MESH : Humans, MESH : Follow-Up Studies, MESH : Disease Progression, medicine.disease, MESH : Antiretroviral Therapy, Highly Active, Virology, Infectious Disease Transmission, Vertical, MESH : Pregnancy, Immunology, DNA, Viral, HIV-1, MESH: Female, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [ SDV.IMM.IA ] Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH: Antiretroviral Therapy, Highly Active, Cohort Studies, law, Antiretroviral Therapy, Highly Active, Immunology and Allergy, MESH : RNA, Viral/blood, MESH : Female, 030212 general & internal medicine, adolescents, Pregnancy Complications, Infectious, MESH : Infectious Disease Transmission, Vertical, MESH: Cohort Studies, Polymerase chain reaction, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Real-Time Polymerase Chain Reaction, MESH: HIV Infections/drug therapy, MESH: Infant, Newborn, MESH : HIV-1/genetics, Viral Load, MESH: Infectious Disease Transmission, Vertical, Infectious Diseases, Real-time polymerase chain reaction, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Human Immunodeficiency Virus DNA, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RNA, Viral, Female, MESH: Viral Load, MESH : DNA, Viral/blood, Adolescent, MESH : HIV Infections/drug therapy, MESH : Male, MESH : Real-Time Polymerase Chain Reaction, Biology, Real-Time Polymerase Chain Reaction, MESH : Infant, Newborn, Peripheral blood mononuclear cell, Young Adult, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, cumulative viremia, medicine, MESH : CD4 Lymphocyte Count, MESH: Viremia, 030304 developmental biology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: HIV-1/genetics, Infant, Newborn, MESH: Male, CD4 Lymphocyte Count, MESH : HIV-1/isolation & purification, MESH : HIV-1/drug effects, MESH: HIV-1/drug effects, Follow-Up Studies
Abstract: Background. Our aim was to study the impact of lifelong human immunodeficiency virus (HIV) disease history on the current immune and virological status of perinatally infected patients reaching adulthood. We evaluated blood cell–associated HIV DNA load as an indicator of cell-associated HIV reservoirs and an independent predictor of disease progression. Methods. The ANRS-EP38-IMMIP Study included 93 patients aged 15–24 years who were infected with HIV during the perinatal period. HIV DNA load was quantified by real-time polymerase chain reaction. Results. Eighty-five percent of patients were receiving highly active antiretroviral therapy (HAART), and HIV RNAwas undetectableintheplasmaof75%ofthesepatients.ThemedianHIV DNAloadwas 2.84(interquartilerange, 2.51–3.16) log10 copies per 10 6 peripheral blood mononuclear cells. In patients with viral suppression, HIV DNA load was independently associated with cumulative HIV RNA viremia over the last 5 years. HIV DNA load was negatively correlated with CD4 cell count in patients with active replication but not in those with undetectable HIV RNA. Conclusions. In perinatally infected youths who are successfully treated, sustained viral suppression is associated with a low HIV DNA load. The absence of association between current HIV DNA load and CD4 cell counts suggests that the unique physiological characteristics of pediatric infection persist after adolescence. Clinical Trials Registration. NCT01055873.
Published: 2012

31. Divergent KSHV/HHV-8 subtype D strains in New Caledonia and Solomon Islands, Melanesia

Author: Sylvie Laumond-Barny, Paul M. V. Martin, Françoise Charavay, Olivier Cassar, Jean-Paul Grangeon, Antoine Gessain, Sabine Plancoulaine, Sylviane Bassot, Suzanne Chanteau, Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Nouvelle-Calédonie, Réseau International des Instituts Pasteur (RIIP), Génétique Humaine des Maladies Infectieuses (Inserm U980), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service des actions sanitaires, Direction des affaires sanitaires et sociales de Nouvelle-Calédonie, Olivier Cassar thanks the Institut Pasteur de Nouvelle-Calédonie and the Institut Pasteur International Network for financial support, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Réseau International des Instituts Pasteur ( RIIP ) -Institut Pasteur de Nouvelle-Calédonie, Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), and Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Adolescent, viruses, [SDV]Life Sciences [q-bio], Biology, Antibodies, Viral, 03 medical and health sciences, Virology, Genotype, medicine, Cluster Analysis, Humans, Seroprevalence, Melanesians, Genetic variability, Kaposi's sarcoma, Phylogeny, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, [ SDV ] Life Sciences [q-bio], Molecular epidemiology, Phylogenetic tree, 030306 microbiology, virus diseases, Herpesviridae Infections, Middle Aged, medicine.disease, Infectious Diseases, DNA, Viral, Herpesvirus 8, Human, Female, Melanesia, Primary effusion lymphoma
Abstract: Background KSHV/HHV-8 is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma and most multicentric Castleman's disease cases. KSHV exhibits a high genetic variability comprising five genotypes (A–E). Few data are yet available concerning the situation of KSHV, its genetic variability and the associated diseases in Melanesia. Objectives We performed a study on 626 natives Melanesians from New Caledonia and Vanikoro Island to evaluate KSHV seroprevalence and characterize molecularly the viral strains. Study design Plasma from 343 males and 283 females (age range: 15–86 years, mean age: 60) were tested for KSHV latent antibodies by an immunofluorescence assay (IFA) using BC-3 cells. DNAs extracted from peripheral blood buffy-coat of KSHV seropositive individuals were amplified to obtain a 737-bp fragment of the ORF-K1 gene. Phylogenetic analyses were then performed. Results Among 626 samples, 148 were IFA positive (dilution ≥ 1:80). The overall seroprevalence was 23.6% (25.2% in New Caledonia, 17.5% in Vanikoro). Fifteen (8 men and 7 women, mean age 69 years) out of 148 DNA samples were found PCR positive. All ORF-K1 sequences belonged to KSHV genotype D. A geographic clustering according to the island of origin of KSHV infected persons was clearly observed with sequences from New Caledonia clustering with most Vanuatu strains. Conclusions New Caledonia and Vanikoro are endemic for KSHV with a high diversity of genotype D variants. These strains were probably introduced into New Caledonia during multiple waves of migrations of Melanesian and Polynesian individuals that have colonized this archipelago.
Published: 2012

32. Multicentric Castleman Disease in an HHV8-Infected Child Born to Consanguineous Parents With Systematic Review

Author: Rose-Marie Herbigneaux, Matthias Muszlak, Jean-Pierre Rivière, Stéphane Blanche, Antoine Gessain, Claire Fieschi, Despina Moshous, Vincent Pedergnana, Jean-Laurent Casanova, Yves Reguerre, Capucine Picard, Sabine Plancoulaine, Minji Byun, Jean-Pierre Arnaud, Eric Oksenhendler, Alain Fischer, Danielle Canioni, Sandrine Leroy, Olivier Cassar, Nizar Mahlaoui, Assistance Publique-Hôpitaux de Paris, Service d'Immunologie et d'Hématologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre for Statistics in Medicine, University of Oxford [Oxford], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Mayotte, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Human Genetics of Infectious Diseases, Sandrine Leroy is supported by a grant from the Fondation pour la Recherche Médicale and The French Foreign Office. Sabine Plancoulaine is supported in part by Assistance Publique-Hôpitaux de Paris. The Branches of the Laboratory of Human Genetics of Infectious Diseases at Necker and Rockefeller are supported by grants from Institut National de la Santé et de la Recherche Médicale, University Paris Descartes, the Rockefeller University Center for Clinical and Translational Science (grant 5UL1RR024143-03), the Rockefeller University, the Agence Nationale de la Recherche, the BNP Paribas Foundation, the March of Dimes, and the Dana Foundation. Jean-Laurent Casanova was an International Scholar of the Howard Hughes Medical Institute., Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), University of Oxford, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), CHU Félix Guyon, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, rockefeller university, Institut National de la Santé et de la Recherche Médicale-Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Diderot - Paris 7 ( UPD7 ) -CHU Saint Louis [APHP], and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Consanguinity, Pediatrics, viruses, [SDV]Life Sciences [q-bio], Case Reports, MESH : Herpesviridae Infections/complications, MESH: Herpesviridae Infections/immunology, human herpes virus 8, Consanguinity, 0302 clinical medicine, MESH : Child, systematic review, MESH: Child, MESH: Giant Lymph Node Hyperplasia/pathology, MESH : Female, Child, Children, Immunodeficiency, virus diseases, MESH: Herpesviridae Infections/complications, Herpesviridae Infections, 3. Good health, MESH : Herpesviridae Infections/immunology, 030220 oncology & carcinogenesis, MESH : Consanguinity, Herpesvirus 8, Human, Female, Sarcoma, MESH : Herpesvirus 8, Human, medicine.medical_specialty, multicentric Castleman disease, MESH: Herpesvirus 8, Human, MESH : Giant Lymph Node Hyperplasia/pathology, 03 medical and health sciences, Immunity, 030225 pediatrics, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Humans, MESH : Giant Lymph Node Hyperplasia/complications, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, MESH : Giant Lymph Node Hyperplasia/virology, Castleman Disease, MESH : Humans, nutritional and metabolic diseases, medicine.disease, MESH: Giant Lymph Node Hyperplasia/complications, eye diseases, Pediatrics, Perinatology and Child Health, Multicentric Castleman Disease, business, MESH: Giant Lymph Node Hyperplasia/virology, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Childhood multicentric Castleman disease (MCD) is a rare and unexplained lymphoproliferative disorder. We report a human herpesvirus-8 (HHV-8)-infected child, born to consanguineous Comorian parents, who displayed isolated MCD in the absence of any known immunodeficiency. We also systematically review the clinical features of the 32 children previously reported with isolated and unexplained MCD. The characteristics of this patient and the geographic areas of origin of most previous cases suggest that pediatric MCD is associated with HHV-8 infection. Moreover, as previously suggested for Kaposi sarcoma, MCD in childhood may result from inborn errors of immunity to HHV-8 infection.
Published: 2012

33. Nanopore sequencing of a monkeypox virus strain isolated from a pustular lesion in the Central African Republic

Author: Mathias, Vandenbogaert, Aurélia, Kwasiborski, Ella, Gonofio, Stéphane, Descorps-Declère, Benjamin, Selekon, Andriniaina Andy, Nkili Meyong, Rita Sem, Ouilibona, Antoine, Gessain, Jean-Claude, Manuguerra, Valérie, Caro, Emmanuel, Nakoune, Nicolas, Berthet, Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP), Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherches Médicales de Franceville (CIRMF), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), This study was supported by the World Organisation for Animal Health (OIE) through the European Union (capacity building and surveillance for Ebola virus disease, EBO-SURSY, project reference: FOOD/2016/379-660). This project was also supported by Agence National de la Recherche (Grant AFRIPOX) as well as by the Chinese Academy of Sciences, a Shanghai Municipal Science and Technology Major Project (Grant No. 2019SHZDZX02) and External Cooperation Program of Chinese Academy of Sciences (Grant No. 153211KYSB20160001)., and ANR-19-CE35-0011,AFRIPOX,Etude 'One Health' sur le monkeypox: infection humaine, réservoir animal, écologie de la maladie et outils diagnostiques(2019)
Subjects: Central African Republic, Nanopore Sequencing, Multidisciplinary, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, High-Throughput Nucleotide Sequencing, Humans, Monkeypox, Monkeypox virus, Phylogeny
Abstract: Monkeypox is an emerging and neglected zoonotic disease whose number of reported cases has been gradually increasing in Central Africa since 1980. This disease is caused by the monkeypox virus (MPXV), which belongs to the genus Orthopoxvirus in the family Poxviridae. Obtaining molecular data is particularly useful for establishing the relationships between the viral strains involved in outbreaks in countries affected by this disease. In this study, we evaluated the use of the MinION real-time sequencer as well as different polishing tools on MinION-sequenced genome for sequencing the MPXV genome originating from a pustular lesion in the context of an epidemic in a remote area of the Central African Republic. The reads corresponding to the MPXV genome were identified using two taxonomic classifiers, Kraken2 and Kaiju. Assembly of these reads led to a complete sequence of 196,956 bases, which is 6322 bases longer than the sequence previously obtained with Illumina sequencing from the same sample. The comparison of the two sequences showed mainly indels at the homopolymeric regions. However, the combined use of Canu with specific polishing tools such as Medaka and Homopolish was the best combination that reduced their numbers without adding mismatches. Although MinION sequencing is known to introduce a number of characteristic errors compared to Illumina sequencing, the new polishing tools allow a better-quality MinION-sequenced genome, thus to be used to help determine strain origin through phylogenetic analysis.
Published: 2022

34. Clinical and Public Health Implications of Human T-Lymphotropic Virus Type 1 Infection

Author: Nicolas Legrand, Skye McGregor, Rowena Bull, Sahar Bajis, Braulio Mark Valencia, Amrita Ronnachit, Lloyd Einsiedel, Antoine Gessain, John Kaldor, Marianne Martinello, University of New South Wales [Sydney] (UNSW), Royal Prince Alfred Hospital [Sydney, Australia], Central Australian Health Service [Alice Springs], Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Adult, Microbiology (medical), clinical methods, MESH: Paraparesis, Tropical Spastic, human T-cell leukemia virus, sexually transmitted diseases, viruses, [SDV]Life Sciences [q-bio], Review, immune system diseases, oncogenic virus, hemic and lymphatic diseases, MESH: HTLV-I Infections, diagnostics, Humans, Leukemia-Lymphoma, Adult T-Cell, MESH: Leukemia-Lymphoma, Adult T-Cell, clinical therapeutics, Human T-lymphotropic virus 1, MESH: Human T-lymphotropic virus 1, MESH: Humans, General Immunology and Microbiology, pathogenesis, public health, Public Health, Environmental and Occupational Health, virus diseases, MESH: Adult, HTLV-I Infections, Paraparesis, Tropical Spastic, virology, Infectious Diseases, epidemiology, MESH: Public Health
Abstract: International audience; Human T-lymphotropic virus type 1 (HTLV-1) is estimated to affect 5 to 10 million people globally and can cause severe and potentially fatal disease, including adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The burden of HTLV-1 infection appears to be geographically concentrated, with high prevalence in discrete regions and populations. While most high-income countries have introduced HTLV-1 screening of blood donations, few other public health measures have been implemented to prevent infection or its consequences. Recent advocacy from concerned researchers, clinicians, and community members has emphasized the potential for improved prevention and management of HTLV-1 infection. Despite all that has been learned in the 4 decades following the discovery of HTLV-1, gaps in knowledge across clinical and public health aspects persist, impeding optimal control and prevention, as well as the development of policies and guidelines. Awareness of HTLV-1 among health care providers, communities, and affected individuals remains limited, even in countries of endemicity. This review provides a comprehensive overview on HTLV-1 epidemiology and on clinical and public health and highlights key areas for further research and collaboration to advance the health of people with and at risk of HTLV-1 infection.
Published: 2022

35. Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection

Author: Isabelle Bally, Judith A. Burger, Rogier W. Sanders, M. Buisson, Wesley Gros, Pascal Poignard, Axelle Amen, Roger Le Grand, Daphna Fenel, Francis Relouzat, Guy Schoehn, Camille Bouillier, Vanessa Contreras, Nicole M. Thielens, Julien Lemaitre, Franck Fieschi, Guidenn Sulbaran, Sylvie van der Werf, Anne-Sophie Gallouet, Nathalie Dereuddre-Bosquet, Winfried Weissenhorn, Romain Marlin, Michel Thépaut, Thibaut Naninck, Delphine Guilligay, Sebastian Dergan Dylon, Marit J. van Gils, Pauline Maisonnasse, Meliawati Poniman, 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), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Department of Medical Microbiology and Infection Prevention [Amsterdam], University of Amsterdam [Amsterdam] (UvA), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), This work acknowledges support by the European Union's Horizon 2020 research and innovation program under grant agreement no. 681032, H2020 EHVA (W.W.), the ANR, RA-Covid-19 (W.W. and R.l.G.), and the CNRS (W.W.). W.W. acknowledges access to the platforms of the Grenoble Instruct-ERIC center (IBS and ISBG, UMS 3518 CNRS-CEA-UGA-EMBL) within the Grenoble Partnership for Structural Biology (PSB), with support from FRISBI (ANR-10-INBS-05-02) and GRAL, a project of the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS (ANR-17-EURE-0003). The IBS acknowledges integration into the Interdisciplinary Research Institute of Grenoble (IRIG, CEA) and financial support from CEA, CNRS, and UGA. The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the Program Investissements d’Avenir, managed by the National Research Agency (ANR) under reference ANR-11-INBS-0008. The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT’s facilities and imaging technologies. The NHP study received financial support from REACTing, the Fondation pour la Recherche Médicale (AM-CoV-Path), and the European Infrastructure TRANSVAC2 (730964). We acknowledge support from CoVIC, supported by the Bill and Melinda Gates Foundation. The virus stock was obtained through the EVAg platform (https://www.european-virus-archive.com/), funded by H2020 (653316)., ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), European Project: 681032,H2020,H2020-PHC-2015-single-stage_RTD,EHVA(2016), European Project: 730964, H2020, RIA,H2020-INFRAIA-2016-1,TRANSVAC2(2017), European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), Thomas, Frank, Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID, CBH-EUR-GS - - CBH-EUR-GS2017 - ANR-17-EURE-0003 - EURE - VALID, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, European HIV Vaccine Alliance (EHVA): a EU platform for the discovery and evaluation of novel prophylactic and therapeutic vaccine candidates - EHVA - - H20202016-01-01 - 2020-12-31 - 681032 - VALID, European Vaccine Research and Development Infrastructure - TRANSVAC2 - - H2020, RIA2017-05-01 - 2022-04-30 - 730964 - VALID, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Graduate School, Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), platforms of the Grenoble Instruct-ERIC center (IBS and ISBG, and UMS 3518 CNRS-CEA-UGA-EMBL)
Subjects: Male, [SDV]Life Sciences [q-bio], MESH: Spike Glycoprotein, Coronavirus, Antibodies, Viral, Neutralization, MESH: Antibodies, Neutralizing, MESH: Chlorocebus aethiops, Chlorocebus aethiops, MESH: COVID-19, antibodies, MESH: Animals, MESH: Treatment Outcome, MESH: Immunoglobulin G, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Vaccination, Antibody titer, formaldehyde cross-linking, protection, S glycoprotein, medicine.anatomical_structure, Treatment Outcome, MESH: COVID-19 Vaccines, MESH: HEK293 Cells, Spike Glycoprotein, Coronavirus, Antibody, MESH: Pandemics, COVID-19 Vaccines, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], macaques, T cell, MESH: Vero Cells, Biology, General Biochemistry, Genetics and Molecular Biology, Virus, Article, Immunity, medicine, Animals, Humans, MESH: SARS-CoV-2, Vaccines, Virus-Like Particle, MESH: Immunoglobulin A, MESH: Vaccines, Virus-Like Particle, Pandemics, Vero Cells, B cells, MESH: Humans, SARS-CoV-2, COVID-19, MESH: Vaccination, Th1 Cells, Virology, Antibodies, Neutralizing, immunity, MESH: Male, Immunoglobulin A, Disease Models, Animal, Macaca fascicularis, HEK293 Cells, Immunization, MESH: Macaca fascicularis, MESH: Th1 Cells, Immunoglobulin G, Liposomes, biology.protein, MESH: Liposomes, nanoparticles, MESH: Disease Models, Animal, MESH: Antibodies, Viral
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused an ongoing global health crisis. Here, we present as a vaccine candidate synthetic SARS-CoV-2 spike (S) glycoprotein-coated lipid vesicles that resemble virus-like particles. Soluble S glycoprotein trimer stabilization by formaldehyde cross-linking introduces two major inter-protomer cross-links that keep all receptor-binding domains in the “down” conformation. Immunization of cynomolgus macaques with S coated onto lipid vesicles (S-LVs) induces high antibody titers with potent neutralizing activity against the vaccine strain, Alpha, Beta, and Gamma variants as well as T helper (Th)1 CD4+-biased T cell responses. Although anti-receptor-binding domain (RBD)-specific antibody responses are initially predominant, the third immunization boosts significant non-RBD antibody titers. Challenging vaccinated animals with SARS-CoV-2 shows a complete protection through sterilizing immunity, which correlates with the presence of nasopharyngeal anti-S immunoglobulin G (IgG) and IgA titers. Thus, the S-LV approach is an efficient and safe vaccine candidate based on a proven classical approach for further development and clinical testing., Graphical abstract, Sulbaran et al. find that formaldehyde cross-linked S lipid nanoparticles induce potent neutralizing antibody titers upon cynomolgus macaque vaccination. Notably, vaccinated animals develop sterilizing immunity as highlighted upon virus challenge. Thus, the study provides a path to induce sterilizing immunity correlating with mucosal immune responses, which are desired to prevent virus spreading.
Published: 2022

36. Excretion of Cell-Free and Cell-Associated Zika Virus into Breast Milk of Infected Dams and Identification of Antiviral Factors

Author: Sophie Desgraupes, Patricia Jeannin, Antoine Gessain, Pierre-Emmanuel Ceccaldi, Aurore Vidy, 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), S.D. was the recipient of a PhD fellowship from the French ministry of education and research for this project, and We thank Mathieu Hubert (Institut Pasteur) for his participation in the milk collection during the last experiment, Philippe Afonso (Institut Pasteur) for improving the manuscript, Emeline Perthame (Bioinformatics and Biostatistics HUB, Institut Pasteur) for improving the statistical analysis and Valérie Choumet (Institut Pasteur) for helpful advice.
Subjects: MESH: Antiviral Agents, breastfeeding, mother-to-child transmission, milk cells, antiviral, fatty acids, MESH: Zika Virus, Antiviral Agents, Biological Factors, Mice, MESH: Zika Virus Infection, MESH: Pregnancy, Pregnancy, Virology, Animals, Humans, MESH: Animals, MESH: Mice, MESH: Humans, MESH: Milk, Human, Milk, Human, Zika Virus Infection, Zika Virus, MESH: Satellite Viruses, Infectious Disease Transmission, Vertical, MESH: Infectious Disease Transmission, Vertical, Infectious Diseases, Satellite Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Biological Factors, Female, MESH: Female
Abstract: International audience; Zika virus (ZIKV) is a mosquito-borne RNA virus belonging to the Flavivirus genus of the Flaviviridae family. During the 60 years following its discovery in 1947, ZIKV caused little concern for public health as the associated infection was reported as mostly asymptomatic or inducing mild symptoms. However, since 2013, severe neurological symptoms have been associated with ZIKV infection, compelling the World Health Organization to declare a Public Health Emergency of International Concern. Among those symptoms, neurological birth defects may affect children born to mothers infected during pregnancy. Additionally, during the past 8 years, ZIKV transmission through breastfeeding has repeatedly been suggested in epidemiological studies and demonstrated on a mouse model by our team. To better understand the biological factors controlling ZIKV transmission through breastfeeding, we investigated the nature of the viral entities excreted in the breast milk of infected dams and evaluated viral transmission to breastfed pups. We show that both cell-free and cell-associated virus is excreted into breast milk and that ZIKV is efficiently transmitted to the breastfed pups. Additionally, we studied murine breast milk cell types, and identified a majority of mammary luminal cells. Finally, we investigated the effect on ZIKV infectivity of several breast milk components that are antiviral against different viruses such as lactoferrin (LF) and lactalbumin (LA), or free fatty acids (FFA). We showed no effect of LF and LA, whereas FFA inactivated the virus. These results bring new insight concerning the mechanisms of ZIKV transmission during breastfeeding and identify biological factors modulating it. These elements should be considered in risk assessment of ZIKV mother-to-child transmission
Published: 2022

37. Reply to: Oncolytic Viral Therapy for Malignant Pleural Mesothelioma

Author: Clément Meiller, Nicolas Boisgerault, Tiphaine Delaunay, Marc Grégoire, Marion Grard, Stefano Caruso, Jean-François Fonteneau, Jaafar Bennouna, Didier Jean, Frédéric Tangy, Emanuela Felley-Bosco, Christophe Blanquart, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), University hospital of Zurich [Zurich], Service de pneumologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), 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), ANR-16-CE18-0016,OncoMeVax,Un virus de la rougeole modifié pour traiter le cancer(2016), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), Bernardo, Elizabeth, Un virus de la rougeole modifié pour traiter le cancer - - OncoMeVax2016 - ANR-16-CE18-0016 - AAPG2016 - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, 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 d'Angers (UA)-Université de Nantes (UN)-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)-Université d'Angers (UA)-Université de Nantes (UN)-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), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Zurich, Jean, Didier, and École Pratique des Hautes Études (EPHE)
Subjects: Mesothelioma, Pulmonary and Respiratory Medicine, Lung Neoplasms, 10255 Clinic for Thoracic Surgery, Pleural Neoplasms, 610 Medicine & health, [SDV.CAN]Life Sciences [q-bio]/Cancer, Measles virus, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Oncolytic immunotherapy, Humans, Medicine, Viral therapy, ComputingMilieux_MISCELLANEOUS, Sequence Deletion, 030304 developmental biology, 0303 health sciences, MESH: Type I interferon, MESH: Mesothelioma, biology, business.industry, Pleural mesothelioma, Homozygote, MESH: Gene homozygous deletion, biology.organism_classification, Oncolytic virus, Oncolytic Viruses, Oncology, 2740 Pulmonary and Respiratory Medicine, 030220 oncology & carcinogenesis, Interferon Type I, Cancer research, 2730 Oncology, business, MESH: Measles virus, Interferon type I, medicine.drug
Abstract: International audience
Published: 2020

38. HTLV‐1 and Neurological‐Associated Disease

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), Fabrice Chretien, Kum Thong Wong, Leroy R. Sharer, Katy Keohane, Francoise Gray, International Society of Neuropathology, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: 0303 health sciences, business.industry, virus diseases, Disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology, Medicine, business, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: International audience; Human T-cell leukemia/lymphoma virus-1 (HTLV-1), the first human oncoretrovirus, is the etiological agent of a chronic neuromyelopathy named “tropical spastic paraparesis/HTLV-1–associated myelopathy (TSP/HAM). At least 5–10 million individuals are infected worldwide. The areas of highest prevalence are southwestern Japan and parts of the Caribbean, South America, intertropical Africa, and the Middle East. The lifetime risk of developing TSP/HAM in HTLV-1 carriers is estimated at 0.25–4%, depending on the endemic area. The neurological characteristics include spasticity or hyper-reflexia of the lower limbs, urinary bladder disturbances often with lower limb muscle weakness, sensory disturbance, and low back pain. TSP/HAM pathology is characterized by chronic inflammation with perivascular lymphocyte cuffs and mild parenchymal lymphocytic infiltrates, foamy macrophages, astrocyte proliferation, and fibrillary gliosis. Pyramidal tract degenerative lesions with myelin and axonal loss are observed, mainly in the lower thoracic spinal cord; these are linked to inflammatory foci in the CNS. The treatment of TSP/HAM remains largely symptomatic because there is no current disease-modifying therapy with definite long-term clinical benefit.
Published: 2020

39. Plasma antibodies from humans infected with zoonotic simian foamy virus do not inhibit cell-to-cell transmission of the virus despite binding to the surface of infected cells

Author: Mathilde Couteaudier, Thomas Montange, Richard Njouom, Chanceline Bilounga-Ndongo, Antoine Gessain, Florence Buseyne, 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), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Ministère de la Santé Publique [Yaoundé, Cameroun], This work was supported by the Agence Nationale de la Recherche (REEMFOAMY project, ANR 15-CE-15-0008-01, A.G.), Institut Pasteur (PTR2020-353 ZOOFOAMENV, F.B.), and Agence Nationale de la Recherche (Grant Intra Labex, ANR-10-LABX62-IBEID, F.B.)., ANR-15-CE15-0008,REEMFOAMY,L'infection humaine par les virus foamy simiens zoonotiques : rôle des facteurs virologiques et immunologiques dans la restrcition de l'emergence virale(2015), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: MESH: Humans, Gorilla gorilla, MESH: Gorilla gorilla, [SDV]Life Sciences [q-bio], Immunology, DNA Viruses, Hominidae, MESH: Simian foamy virus, Microbiology, MESH: DNA Viruses, Simian foamy virus, MESH: Hominidae, MESH: Retroviridae Infections, MESH: Spumavirus, Virology, Genetics, Animals, Humans, Spumavirus, MESH: Animals, Parasitology, Molecular Biology, Retroviridae Infections
Abstract: Zoonotic simian foamy viruses (SFV) establish lifelong infection in their human hosts. Despite repeated transmission of SFV from nonhuman primates to humans, neither transmission between human hosts nor severe clinical manifestations have been reported. We aim to study the immune responses elicited by chronic infection with this retrovirus and previously reported that SFV-infected individuals generate potent neutralizing antibodies that block cell infection by viral particles. Here, we assessed whether human plasma antibodies block SFV cell-to-cell transmission and present the first description of cell-to-cell spreading of zoonotic gorilla SFV. We set-up a microtitration assay to quantify the ability of plasma samples from 20 Central African individuals infected with gorilla SFV and 9 uninfected controls to block cell-associated transmission of zoonotic gorilla SFV strains. We used flow-based cell cytometry and fluorescence microscopy to study envelope protein (Env) localization and the capacity of plasma antibodies to bind to infected cells. We visualized the cell-to-cell spread of SFV by real-time live imaging of a GFP-expressing prototype foamy virus (CI-PFV) strain. None of the samples neutralized cell-associated SFV infection, despite the inhibition of cell-free virus. We detected gorilla SFV Env in the perinuclear region, cytoplasmic vesicles and at the cell surface. We found that plasma antibodies bind to Env located at the surface of cells infected with primary gorilla SFV strains. Extracellular labeling of SFV proteins by human plasma samples showed patchy staining at the base of the cell and dense continuous staining at the cell apex, as well as staining in the intercellular connections that formed when previously connected cells separated from each other. In conclusion, SFV-specific antibodies from infected humans do not block cell-to-cell transmission, at leastin vitro, despite their capacity to bind to the surface of infected cells.Trial registration: Clinical trial registration:www.clinicaltrials.gov,https://clinicaltrials.gov/ct2/show/NCT03225794/.
Published: 2022

40. 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

41. High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis

Author: Yves Plumelle, Antoine Gessain, India Leclercq, Antoine Talarmin, Anne-Sophie Gabet, Michel Joubert, Eric Wattel, Arnaud Leroy, Franck Mortreux, E. Clity, Virologie et pathogenèse virale (VPV), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Service d'hématologie [Fort de France], Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Epidémiologie des virus oncogènes, Institut Pasteur [Paris], Université de Mons-Hainaut, This work was supported by a grant from the Association pour la Recherche sur le Cancer and from the ComiteÂ deÂ partemental de la Drome de la Ligue Nationale Contre le Cancer. ASG was supported by a bursary from the centre LeÂ on BeÂ rard, I Leclerq and F Montreux were supported by a bursary from the MinisteÁ re de l'Enseignement SupeÂ rieur et de la Recherche. We would like to thank Pr Wattre and collaborators who kindly welcomed us in their laboratories for DNA extraction, digestion, ligation and PCR. We would also like to thank Marie-Dominique Reynaud for assistance., Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Madagascar, Service d'hématologie, Cellule d'Intervention Biologique d'Urgence (CIBU), Université Paris Diderot - Paris 7 (UPD7), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Institut Guyanais de Dermatologie Tropicale, EA 2188, Centre Hospitalier Andrée Rosemon, Service de Pathologie, Hôpital Femme-Enfant-Adolescent-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lille-UNICANCER, Institut Pasteur [Paris] (IP), Université Paris Descartes - Paris 5 ( UPD5 ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur de Madagascar-Réseau International des Instituts Pasteur ( RIIP ), Cellule d'Intervention Biologique d'Urgence ( CIBU ), Université Paris Diderot - Paris 7 ( UPD7 ), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] ( IBMM ), Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Hôpital Femme-Enfant-Adolescent-Centre hospitalier universitaire de Nantes ( CHU Nantes ), and Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Femme-Enfant-Adolescent
Subjects: Male, Cancer Research, viruses, T-Lymphocytes, T-cell leukemia, Proviruses/genetics/*physiology, Lymphocyte Activation, Virus Replication, Polymerase Chain Reaction, Acyclovir/*pharmacology, 0302 clinical medicine, Proviruses, immune system diseases, hemic and lymphatic diseases, Thiabendazole, 80 and over, Thiabendazole/therapeutic use, Non-U.S. Gov't, OCIS 000.1430, Child, T-Lymphocytes/cytology/immunology/*virology, Strongyloidiasis/blood/drug therapy/*virology, Aged, 80 and over, 0303 health sciences, Human T-lymphotropic virus 1, Antinematodal Agents, virus diseases, Middle Aged, Viral Load, 3. Good health, medicine.anatomical_structure, Strongyloidiasis, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Carrier State, Female, medicine.symptom, Viral load, Adult, Adolescent, T cell, Biology, Human T-lymphotropic virus 1/genetics/*physiology, Research Support, Asymptomatic, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Adult T-cell leukemia/lymphoma, Strongyloides stercoralis, 03 medical and health sciences, Genetics, medicine, Animals, Humans, Molecular Biology, 030304 developmental biology, Aged, medicine.disease, biology.organism_classification, Virology, Clone Cells, Immunology, Carrier State/blood/virology, Asymptomatic carrier, Antinematodal Agents/therapeutic use
Abstract: International audience; Adult T cell leukemia (ATLL) develops in 3 - 5% of HTLV-1 carriers after a long period of latency during which a persistent polyclonal expansion of HTLV-1 infected lymphocytes is observed in all individuals. This incubation period is significantly shortened in HTLV-1 carrier with Strongyloides stercoralis (Ss) infection, suggesting that Ss could be a cofactor of ATLL. As an increased T cell proliferation at the asymptomatic stage of HTLV-1 infection could increase the risk of malignant transformation, the effect of Ss infection on infected T lymphocytes was assessed in vivo in HTLV-1 asymptomatic carriers. After real-time quantitative PCR, the mean circulating HTLV-1 proviral load was more than five times higher in HTLV-1 carriers with strongyloidiasis than in HTLV-1+ individuals without Ss infection (P
Published: 2000

42. Infection des cellules endothéliales humaines par le virus Zika : rôle des claudines dans l'infection et comme modèles de développement de molécules thérapeutiques

Author: Zoladek, Jim, 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), Université Paris Cité, and Philippe Afonso
Subjects: Barrière hémato-encéphalique, Virus Zika, Claudine, Flavivirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Antiviral peptide, Peptide antiviral, Endothelium, Endothélium, Infection, Zika virus, Blood-brain barrier, Claudin
Abstract: Zika virus (ZIKV) is an arbovirus belonging to the Flavivirus genus of the Flaviviridae family. ZIKV emergence in the Pacific islands and in the Americas in the xxx led to demonstrate that ZIKV infection was associated with several neuropathologies including Guillain-Barré syndrome and Zika congenital syndrome. During these pathologies, ZIKV is detected in the central nervous system (CNS) evidencing the neuroinvasive capacity of the virus. The CNS is protected against blood-borne pathogens by several anatomical barriers including the blood-brain barrier (BBB), which is composed of different cell types including endothelial cells that form a continuous capillary sealed with tight-junctions. Crossing the BBB could be the result of the productive infection of these endothelial cells. Hence, we focused our study on the mechanisms of such an infection. In vitro, we found a differential susceptibility to ZIKV infection of a human brain microvascular endothelial cell line (hCMEC/D3) in two commercially available culture media. We discovered that the gene coding for claudin-7 (CLDN7) was overexpressed when the cells were the most susceptible to ZIKV infection. Moreover, the knock down (KD) of CLDN7 using lentiviral vectors containing shRNAs reduced the susceptibility to ZIKV infection. We confirmed these findings in other endothelial cells originating from umbilical or the bone marrow veins. Interestingly, even if susceptibility to the infection was altered in CLDN7-KD cells, their ability to bind and internalize viral particles remained unchanged. This suggests that CLDN7 is involved in late steps of the infection (sorting of virions within in the endosomal network or viral fusion to the endosomal membrane). On the contrary, CLDN7-KD had no effect on epithelial cells, suggesting compensation mechanisms or other pathways of infection in these tissues. Based on these observations, we next studied claudin-derived (CLDN1 and CLDN7) peptides and their ability to inhibit ZIKV infection. We discovered that claudin N-terminus-derived peptides had inhibitory properties. Our results suggest that these peptides inhibit viral fusion by directly interacting with the viral particles. We also found that the peptides were broad-spectrum antivirals since they can inhibit in vitro infection of other flaviviruses (i.e. yellow fever virus and Japanese encephalitis virus). This work lead to the discovery of CLDN7-involvement in ZIKV infection, the role of claudins had not been shown for ZIKV. Moreover, our characterization of a broad-spectrum inhibitory peptide helps in the understanding of the infection mechanisms and could serve as a template for therapeutic drug development.; Le virus Zika (ZIKV) est un arbovirus du genre Flavivirus et de la famille des Flaviviridae. Son émergence dans la région Pacifique et en Amérique depuis 2007 a permis d'établir un lien entre l'infection par ZIKV et des pathologies neurologiques, telles que le syndrome de Guillain-Barré et la microcéphalie liée à Zika. Ces pathologies sont associées à la détection de virus dans le système nerveux central (SNC) des patients, ce qui traduit une capacité neuroinvasive du virus. Le SNC est protégé contre les pathogènes présentes dans le sang par un ensemble d'interfaces dont la barrière hémato-encéphalique (BHE). Celle-ci est constituée de différents types cellulaires dont des cellules endothéliales qui forment un capillaire continu à jonctions serrées. L'infection productive des cellules endothéliales cérébrales pourrait constituer un des mécanismes du franchissement de la BHE et donc de la neuroinvasion. Nous nous sommes donc intéressés à l'infection des cellules endothéliales cérébrales par le ZIKV. Nous avons mis en évidence une sensibilité différentielle à l'infection par le ZIKV in vitro des cellules endothéliales cérébrales humaines de la lignée hCMEC/D3 en comparant deux milieux de culture commerciaux. Nous avons observé que le gène codant la claudine-7 (CLDN7) est surexprimé dans les conditions favorisant l'infection. De plus, la baisse d'expression (Knock Down, KD) de CLDN7 par transduction de shARN dans ces cellules à l'aide de vecteurs lentiviraux, réduit la sensibilité au ZIKV. Nous avons confirmé ces observations sur d'autres modèles de cellules endothéliales (de cordon ombilical ou de moelle osseuse). Nous avons observé que, malgré une différence de sensibilité à l'infection des cellules CLDN7-KD, leurs capacités d'adsorption et d'internalisation des particules virales étaient conservées. Ceci suggère donc que CLDN7 participerait aux étapes tardives de l'infection dans les cellules endothéliales (au niveau du sorting des endosomes ou de la fusion avec la membrane cellulaire). En revanche, le KD de CLDN7 n'a eu aucun effet sur l'infection de cellules épithéliales, suggérant des phénomènes de compensation ou l'implication d'autres voies d'infection dans ces tissus. Forts de ces observations, nous avons étudié la capacité de peptides dérivés de séquences de claudines (CLDN1 et CLDN7) à inhiber l'infection par le ZIKV. Nous avons montré que des peptides correspondants à l'extrémité N-terminale des claudines ont un effet inhibiteur sur l'infection. Nos résultats suggèrent que ces peptides inhibent la fusion des membranes en interagissant avec le virion. Nous avons également démontré que ces peptides ont un large spectre d'action antivirale, car ils permettent in vitro d'inhiber l'infection par d'autres Flavivirus tels que le virus de la fièvre jaune ou le virus de l'encéphalite japonaise. Notre travail a permis de mettre en évidence l'importance de CLDN7 dans l'infection par le ZIKV ; le rôle des claudines n'avait pas été montré à ce jour pour ce virus. De plus, notre caractérisation d'un peptide antiviral à large spectre contribue à une meilleure compréhension des mécanismes d'infection et pourrait servir de base de développement de molécules thérapeutiques.
Published: 2021

43. 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

44. Endemicity And Genetic Diversity of Hepatitis Delta Virus Among Pygmies In Cameroon, Central Africa

Author: Yacouba Foupouapouognigni, Antoine Gessain, Onana Boyomo, Richard Njouom, Jacques Delors Mfonkou Toumansie, Université de Yaoundé I, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and This study was funded by the Agence Nationale de Recherche sur le Sida et les Hépatites Virales (Grant ANRS 12366).
Subjects: Hepatitis B virus, Genotype, [SDV]Life Sciences [q-bio], viruses, Zoology, Biology, Genetic diversity, General Biochemistry, Genetics and Molecular Biology, Virus, MESH: Genotype, Seroepidemiologic Studies, parasitic diseases, Prevalence, MESH: Genetic Variation, Cameroon, MESH: Phylogeny, MESH: Prevalence, Phylogeny, Pygmies, MESH: Seroepidemiologic Studies, Hepatitis B Surface Antigens, HEPATITIS DELTA, Genetic Variation, virus diseases, Central africa, General Medicine, MESH: Cameroon, biochemical phenomena, metabolism, and nutrition, MESH: Hepatitis Delta Virus, Hepatitis D, MESH: Hepatitis B Surface Antigens, MESH: Hepatitis B virus, Hepatitis Delta Virus
Abstract: Objective A single study conducted about three decades ago on hepatitis D virus (HDV) infection among Baka pygmies in Cameroon reported a very high anti-HDV antibodies prevalence of 46%, but HDV genetic diversity has not been studied in this population. The genetic diversity of strains from endemic ancient populations may help to understand the origin and evolutionary history of viruses. This study aimed to investigate the HDV seroprevalence and the genetic diversity in three remote Cameroonian Pygmies with chronic HBV infection. Results An unusually high 69% (36/52) level of HDV infection was found among HBsAg-positive pygmies in Cameroon. HDV RNA was detected and sequenced in 38.8% (14/36). The phylogenetic analysis revealed that 9/14 strains (64.3%) were identified and classified as genotype 1 (HDV-1) and 5/14 (35.6%) as genotype 7 (HDV-7), respectively with a bootstrap value of 100%. The further analysis showed the co-circulation of highly diverse HDV genotypes HDV-1 and HDV-7 in this population. These results highlight the endemicity of HDV infection in Central Africa. The highly diverse HDV-1 and HDV-7 in pygmies suggest an African origin of HDV. However, further studies are needed with larger sample size.
Published: 2021

45. Mother-to-Child Transmission of Arboviruses during Breastfeeding: From Epidemiology to Cellular Mechanisms

Author: Sophie, Desgraupes, Mathieu, Hubert, Antoine, Gessain, Pierre-Emmanuel, Ceccaldi, Aurore, Vidy, 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), and No external funding
Subjects: breastfeeding, [SDV]Life Sciences [q-bio], viruses, Review, Arbovirus Infections, Microbiology, Disease Outbreaks, Zika virus, Dengue, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animals, Humans, intestinal epithelium, barrier crossing mechanisms, yellow fever virus, mammary epithelium, Milk, Human, dengue virus, Zika Virus Infection, Colostrum, viral transmission, mother-to-child transmission, virus diseases, biochemical phenomena, metabolism, and nutrition, Infectious Disease Transmission, Vertical, QR1-502, Breast Feeding, Culicidae, arboviruses, Chikungunya Fever, breast milk, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Chikungunya virus, West Nile virus, West Nile Fever
Abstract: International audience; Most viruses use several entry sites and modes of transmission to infect their host (parenteral, sexual, respiratory, oro-fecal, transplacental, transcutaneous, etc.). Some of them are known to be essentially transmitted via arthropod bites (mosquitoes, ticks, phlebotomes, sandflies, etc.), and are thus named arthropod-borne viruses, or arboviruses. During the last decades, several arboviruses have emerged or re-emerged in different countries in the form of notable outbreaks, resulting in a growing interest from scientific and medical communities as well as an increase in epidemiological studies. These studies have highlighted the existence of other modes of transmission. Among them, mother-to-child transmission (MTCT) during breastfeeding was highlighted for the vaccine strain of yellow fever virus (YFV) and Zika virus (ZIKV), and suggested for other arboviruses such as Chikungunya virus (CHIKV), dengue virus (DENV), and West Nile virus (WNV). In this review, we summarize all epidemiological and clinical clues that suggest the existence of breastfeeding as a neglected route for MTCT of arboviruses and we decipher some of the mechanisms that chronologically occur during MTCT via breastfeeding by focusing on ZIKV transmission process.
Published: 2021

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

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

47. Human T-Lymphotropic virus type 1 and human immunodeficiency virus co-infection in rural Gabon

Author: Augustin Mouinga-Ondémé, Larson Boundenga, Ingrid Précilya Koumba Koumba, Antony Idam Mamimandjiami, Abdoulaye Diané, Jéordy Dimitri Engone-Ondo, Delia Doreen Djuicy, Jeanne Sica, Landry Erik Mombo, Antoine Gessain, Avelin Aghokeng Fobang, Centre International de Recherches Médicales de Franceville (CIRMF), Durham University, Université des Sciences et Techniques de Masuku (USTM), Centre de Traitement Ambulatoire [Franceville], Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), and Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)
Subjects: Male, MESH: Gabon, [SDV]Life Sciences [q-bio], Blotting, Western, HIV Infections, MESH: HTLV-I Infections, MESH: Blotting, Western, Humans, Gabon, MESH: Acquired Immunodeficiency Syndrome, Acquired Immunodeficiency Syndrome, Human T-lymphotropic virus 1, Multidisciplinary, MESH: Human T-lymphotropic virus 1, MESH: Humans, MESH: Middle Aged, MESH: Human T-lymphotropic virus 2, MESH: HIV, Coinfection, Human T-lymphotropic virus 2, HIV, MESH: HIV Infections, Middle Aged, HTLV-I Infections, MESH: Male, MESH: Coinfection, Female, MESH: Female
Abstract: Introduction Human T-cell lymphotrophic virus type-1 (HTLV-1) and human immunodeficiency virus (HIV-1) co-infection occur in many populations. People living with HIV-1 and infected with HTLV-1 seem more likely to progress rapidly towards AIDS. Both HTLV-1 and HIV-1 are endemic in Gabon (Central Africa). We investigated HTLV-1 and HIV-1 co-infection in the Haut-Ogooué province, and assessed factors that may favor the rapid evolution and progression to AIDS in co-infected patients. Methods Plasma samples from HTLV-1 patients were tested using ELISA, and positive samples were then tested by western blot assay (WB). We used the polymerase chain reaction to detect HTLV-1 Tax/Rex genes using DNA extracted from the buffy coat of ELISA-positives samples. Results We recruited 299 individuals (mean age 46 years) including 90 (30%) men and 209 (70%) women, all of whom are under treatment at the Ambulatory Treatment Centre of the province. Of these, 45 were ELISA HTLV-1/2 seropositive. According to WB criteria, 21 of 45 were confirmed positive: 20 were HTLV-1 (44%), 1 was HTLV-1/2 (2%), 2 were indeterminate (4%) and 22 were seronegative (49%). PCR results showed that 23 individuals were positive for the Tax/Rex region. Considering both serological and molecular assays, the prevalence of HTLV-1 infection was estimated at 7.7%. Being a woman and increasing age were found to be independent risk factors for co-infection. Mean CD4+ cell counts were higher in HTLV-1/HIV-1 co-infected (578.1 (± 340.8) cells/mm3) than in HIV-1 mono-infected (481.0 (± 299.0) cells/mm3) Individuals. Similarly, the mean HIV-1 viral load was Log 3.0 (± 1.6) copies/ml in mono-infected and Log 2.3 (± 0.7) copies/ml in coinfected individuals. Conclusion We described an overall high prevalence of HTLV-1/HIV-1 co-infection in Gabon. Our findings stress the need of strategies to prevent and manage these co-infections.
Published: 2021

48. Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases

Author: Olivier Hermine, Vahid Asnafi, Izabela Bialuk, Marcia Bellon, Lee Ratner, Ambroise Marçais, Michael N. Petrus, Thomas A. Waldmann, Genoveffa Franchini, Toshiki Watanabe, Antoine Gessain, Masao Matsuoka, Christophe Nicot, Achiléa L. Bittencourt, Lourdes Farre, Veronica Galli, Xue Tao Bai, University of Kansas Medical Center [Kansas City, KS, USA], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Ohio State University [Columbus] (OSU), Hospitalet de Llobregat, Universidade Federal da Bahia (UFBA), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Washington University in Saint Louis (WUSTL), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Kyoto University, Kumamoto University, The University of Tokyo (UTokyo), and This work was supported by grant R01CA201309 to Christophe Nicot.
Subjects: 0301 basic medicine, MESH: Neoplasm Proteins, Cancer Research, MESH: Paraparesis, Tropical Spastic, Lymphoma, [SDV]Life Sciences [q-bio], viruses, T-cell leukemia, Bisulfite sequencing, Tax, MESH: Acid Anhydride Hydrolases, Epigenesis, Genetic, TSP/HAM, 0302 clinical medicine, MESH: DNA Methylation, FHIT, immune system diseases, hemic and lymphatic diseases, Tropical spastic paraparesis, Leukemia-Lymphoma, Adult T-Cell, MESH: Epigenesis, Genetic, MESH: Leukemia-Lymphoma, Adult T-Cell, Càncer, RC254-282, Cancer, Leukemia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Epigenetic, virus diseases, Leucèmia, TSP, Paraparesis, Tropical Spastic, Acid Anhydride Hydrolases, Neoplasm Proteins, Oncology, 030220 oncology & carcinogenesis, Disease Progression, Molecular Medicine, MESH: Disease Progression, Epigenetics, Tumor suppressor gene, Biology, ATLL, Methylation, 03 medical and health sciences, MESH: HTLV-I Infections, medicine, Humans, Epimutation, neoplasms, Retrospective Studies, MESH: Humans, Research, MESH: Retrospective Studies, DNA Methylation, medicine.disease, Epigenètica, HTLV-I Infections, HAM, 030104 developmental biology, ATL, HTLV-1, Cancer research
Abstract: Background Human T cell Leukemia virus type 1 (HTLV-I) is etiologically linked to adult T cell leukemia/lymphoma (ATL) and an inflammatory neurodegenerative disease called HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP). The exact genetic or epigenetic events and/or environmental factors that influence the development of ATL, or HAM/TSP diseases are largely unknown. The tumor suppressor gene, Fragile Histidine Triad Diadenosine Triphosphatase (FHIT), is frequently lost in cancer through epigenetic modifications and/or deletion. FHIT is a tumor suppressor acting as genome caretaker by regulating cellular DNA repair. Indeed, FHIT loss leads to replicative stress and accumulation of double DNA strand breaks. Therefore, loss of FHIT expression plays a key role in cellular transformation. Methods Here, we studied over 400 samples from HTLV-I-infected individuals with ATL, TSP/HAM, or asymptomatic carriers (AC) for FHIT loss and expression. We examined the epigenetic status of FHIT through methylation specific PCR and bisulfite sequencing; and correlated these results to FHIT expression in patient samples. Results We found that epigenetic alteration of FHIT is specifically found in chronic and acute ATL but is absent in asymptomatic HTLV-I carriers and TSP/HAM patients’ samples. Furthermore, the extent of FHIT methylation in ATL patients was quantitatively comparable in virus-infected and virus non-infected cells. We also found that longitudinal HTLV-I carriers that progressed to smoldering ATL and descendants of ATL patients harbor FHIT methylation. Conclusions These results suggest that germinal epigenetic mutation of FHIT represents a preexisting mark predisposing to the development of ATL diseases. These findings have important clinical implications as patients with acute ATL are rarely cured. Our study suggests an alternative strategy to the current “wait and see approach” in that early screening of HTLV-I-infected individuals for germinal epimutation of FHIT and early treatment may offer significant clinical benefits.
Published: 2021

49. Risk factors for seasonal influenza virus detection in stools of patients consulting in general practice for acute respiratory infections in France, 2014‐2016

Author: Alessandra Falchi, Pierre-Emmanuel Ceccaldi, Thomas Hanslik, Sylvie van der Werf, Lisandru Capai, Thierry Blanchon, Shirley Masse, Laëtitia Minodier, Rémi N. Charrel, Laboratoire de Virologie [UNIV Corse-Inserm] (EA7310), Université Pascal Paoli (UPP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Université Sorbonne Paris Cité (USPC), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-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)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], École des Hautes Études en Santé Publique [EHESP] (EHESP), Assistance Publique - Hôpitaux de Marseille (APHM), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Aix Marseille Université (AMU), Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pascal Paoli (UPP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Génétique moléculaire des virus à ARN ((U-Pasteur_ 2 / UMR_3569))
Subjects: Male, Epidemiology, [SDV]Life Sciences [q-bio], General Practice, Antibiotics, 030312 virology, influenza virus, Feces, Risk Factors, Nasopharynx, Medicine, Prospective Studies, Respiratory system, Child, Respiratory Tract Infections, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Gastrointestinal tract, Respiratory infection, Middle Aged, Orthomyxoviridae, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, Original Article, Female, France, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, medicine.drug_class, enteric pathogens, stool samples, Virus, Young Adult, 03 medical and health sciences, Internal medicine, Influenza, Human, Humans, Clinical significance, Aged, business.industry, Infant, Newborn, Public Health, Environmental and Occupational Health, Infant, Original Articles, Odds ratio, Virology, Confidence interval, Cross-Sectional Studies, gastrointestinal symptoms, general practitioner, acute respiratory infection, business
Abstract: BACKGROUND: Previous studies reported detection of influenza RNA in stools of patients with seasonal influenza infection. While this detection may have a clinical significance, other factors may influence the stool positivity for influenza viruses. OBJECTIVES: The objective of this study was to investigate demographical, clinical, and microbiological factors which could favor the presence of influenza viral RNA in the stools of patients with laboratory-confirmed influenza infection. METHODS: Acute respiratory infection (ARI) patients were enrolled by general practitioners (GP) during two winter seasons (2014-2016). Nasopharyngeal swabs, stool specimens, and clinical data were collected. Samples were tested for 12 respiratory pathogen groups (nasopharyngeal and stool specimens) and for 12 enteric pathogens (stool specimens). RESULTS: Among the 331 patients with ARI enrolled by GP, 114 (34.4%) presented influenza infection. Influenza RNA was detected in stool samples of 21% (24/114) of the 114 stool specimens analyzed. Hospitalization (adjusted odds ratio (aOR) = 7.8 (95% confidence interval (CI)) [1.7-33.7], P = .02), age between 45 and 64 years (aOR = 4.8 [1.7-14.5], P = .01), consumption of raw shellfish and/or mollusks (aOR = 16.7 [3.6-90.9], P = .00), and use of antibiotics (aOR = 6.4 [2.1-19.8], P = .006) or antiviral treatment (aOR = 7.4 [1.9-29], P = .01) were significantly associated with an increased odds of the detection of influenza RNA in stools. Among the 24 stool samples subjected to viral isolation, no one showed virus growth. CONCLUSIONS: These findings will be useful to studies investigating the dissemination route of influenza viruses to gastrointestinal tract.
Published: 2019

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

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

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