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Start Over Author "Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]" Journal plos pathogens
2 results on '"Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]"'

1. Proliferative memory SAMHD1low CD4+ T cells harbour high levels of HIV-1 with compartmentalized viral populations

Author

Constance Delaugerre, Antoine Chaillon, Yves Levy, Olivier Schwartz, Joudy Alameddine, Davey M. Smith, Jean-Daniel Lelièvre, Maud Salmona, José-Luiz Lopez Zaragoza, Nabila Seddiki, Nicolas Ruffin, Lylia Hani, Marie-Laure Nere, Physiopathologie et immunothérapies dans l’infection VIH [Créteil] (Inserm U955 Équipe 16), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Vaccine Research Institute (VRI), Department of Medicine [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service d'immunologie clinique et maladies infectieuses [Créteil], Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This study was supported by the Investissement d’Avenir program managed by the ANR under reference ANR-10-LABX-77 and by the Agence Nationale pour la Recherche sur le SIDA et les hepatites virales (ANRS), the Vaccine Research Institute (VRI)., Bodescot, Myriam, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Medicine [Univ California San Diego] (MED - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), and Virus et Immunité - Virus and immunity (CNRS-UMR3569)

Subjects
CD4-Positive T-Lymphocytes, Male, RNA viruses, Physiology, CCR4, HIV Infections, C-C chemokine receptor type 6, CXCR3, Pathology and Laboratory Medicine, Memory T cells, chemistry.chemical_compound, White Blood Cells, Cognition, Learning and Memory, Immunodeficiency Viruses, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animal Cells, Medicine and Health Sciences, Biology (General), Data Management, Staining, 0303 health sciences, T Cells, 030302 biochemistry & molecular biology, Cell Staining, Phylogenetic Analysis, Middle Aged, Phenotype, 3. Good health, Viral Persistence and Latency, Body Fluids, Phylogenetics, Blood, Anti-Retroviral Agents, Medical Microbiology, Viral Pathogens, Viruses, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Lymph, Pathogens, Cellular Types, Anatomy, Research Article, Adult, Computer and Information Sciences, [SDV.IMM] Life Sciences [q-bio]/Immunology, QH301-705.5, Immune Cells, Immunology, Biology, Research and Analysis Methods, Microbiology, Virus, SAM Domain and HD Domain-Containing Protein 1, 03 medical and health sciences, Memory, Virology, Retroviruses, Genetics, Humans, Evolutionary Systematics, Molecular Biology, Microbial Pathogens, 030304 developmental biology, Aged, Taxonomy, Evolutionary Biology, Blood Cells, Lentivirus, Organisms, Biology and Life Sciences, HIV, Cell Biology, RC581-607, Molecular biology, chemistry, Specimen Preparation and Treatment, HIV-1, Cognitive Science, Parasitology, Immunologic diseases. Allergy, Immunologic Memory, DNA, SAMHD1, Neuroscience
Abstract

We previously reported the presence of memory CD4+ T cells that express low levels of SAMHD1 (SAMHD1low) in peripheral blood and lymph nodes from both HIV-1 infected and uninfected individuals. These cells are enriched in Th17 and Tfh subsets, two populations known to be preferentially targeted by HIV-1. Here we investigated whether SAMHD1low CD4+ T-cells harbour replication-competent virus and compartimentalized HIV-1 genomes. We sorted memory CD4+CD45RO+SAMHD1low, CD4+CD45RO+SAMHD1+ and naive CD4+CD45RO-SAMHD1+ cells from HIV-1-infected patients on anti-retroviral therapy (c-ART) and performed HIV-1 DNA quantification, ultra-deep-sequencing of partial env (C2/V3) sequences and phenotypic characterization of the cells. We show that SAMHD1low cells include novel Th17 CCR6+ subsets that lack CXCR3 and CCR4 (CCR6+DN). There is a decrease of the % of Th17 in SAMHD1low compartment in infected compared to uninfected individuals (41% vs 55%, p, Author summary In our previous results we reported that memory CD4+ T cells expressing low levels of SAMHD1 (SAMHD1low) are present in peripheral blood and lymph nodes from HIV-1 infected and uninfected individuals. These cells were enriched in Th17 and Tfh, two populations targeted by HIV-1. Here we used purified memory CD4+CD45RO+SAMHD1low, CD4+CD45RO+SAMHD1+ and naive CD4+CD45RO-SAMHD1+ cells from HIV-1-infected and treated patients to perform cell-associated HIV-1 DNA quantification, p24-producing cells detection, ultra-deep-sequencing of partial env (C2/V3) HIV-1 DNA and further phenotypic characterization. Our results demonstrate that (i) Th17 and CCR6+DN-expressing transcriptional signature of early Th17, two major populations that are susceptible to HIV-1 infection, are present in SAMHD1low cells, and while the former decreased significantly in c-ART HIV-1 infected compared to uninfected individuals, the latter significantly increased; (ii) memory SAMHD1low cells from c-ART patients carry high levels of HIV-1 DNA compared to SAMHD1+ cells, and these levels positively and significantly correlated with Ki67 expression; (iii) memory SAMHD1low cells from patients harbour p24-producing cells; (iv) phylogenetic analyses revealed well-segregated HIV-1 DNA populations with significant compartmentalization between SAMHD1low and SAMHD1+ cells and limited viral exchange. Our data demonstrate that memory SAMHD1low cells contribute to HIV-1 persistence.

Published
2018

2. Potent neutralizing antibodies in humans infected with zoonotic simian foamy viruses target conserved epitopes located in the dimorphic domain of the surface envelope protein

Author

Augustin Mouinga-Ondémé, Dirk Lindemann, Joelle Tobaly-Tapiero, Richard Njouom, Antoine Gessain, Caroline Lambert, Réjane Rua, Florence Buseyne, Julie Gouzil, Léa Richard, Edouard Betsem, Mathilde Couteaudier, Thomas Montange, 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, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Institute of Virology [Dresden], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Centre International de Recherches Médicales de Franceville (CIRMF), CL was personally supported by a doctoral grant from the French government program Investissement d'Avenir, Laboratory of Excellence, Integrative Biology of Emerging Infectious Diseases (LabEx IBEID, http://www.agence-nationale-recherche.fr/ProjetIA-10-LABX-0062). LR was personally supported by the Bourse de l’Ecole Normale Supérieure, Faculté Paris Diderot, http://www.ens.fr/. This work was supported by the Institut Pasteur in Paris, France, the Programme Transversal de Recherche from the Institut Pasteur [PTR#437], https://www.pasteur.fr/fr, and the Agence Nationale de la Recherche [grant ANR-10-LABX-62-IBEID, REEMFOAMY project, ANR 15-CE-15-0008-01, We thank P. Souque, C. Blanc, and P. Afonso for their helpful advice on the molecular biology experiments. We are indebted to Pascale Lesage, Alessia Zamborlini, Ali Saïb, and Olivier Schwartz for helpful discussions. We thank members from the EPVO research unit for discussions and technical advices., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), 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), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), PRES Sorbonne Paris Cité-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technische Universität Dresden (TUD), Centre international de recherches médicales de Franceville (CIRMF), Organisation Mondiale de la Santé (OMS), and ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010)

Subjects
Male, 0301 basic medicine, Physiology, viruses, Artificial Gene Amplification and Extension, Disease Vectors, Blood plasma, Simian, Biochemistry, Epitope, Neutralization, Epitopes, Viral Envelope Proteins, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immune Physiology, Zoonoses, Medicine and Health Sciences, Viral replication, lcsh:QH301-705.5, Mammals, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Immune System Proteins, Eukaryota, virus diseases, Hominidae, Middle Aged, Body Fluids, Polymerase chain reaction, 3. Good health, Blood, Infectious Diseases, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Vertebrates, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Apes, Anatomy, Antibody, Research Article, Primates, Adult, lcsh:Immunologic diseases. Allergy, Gorillas, Pan troglodytes, Immunology, Population, Biology, Research and Analysis Methods, Microbiology, Antibodies, Viral vector, 03 medical and health sciences, Simian foamy virus, Virology, Genetics, Animals, Humans, Amino Acid Sequence, Chimpanzees, Molecular Biology Techniques, education, Molecular Biology, Gene, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Binding Sites, Gorilla gorilla, Co-infections, Organisms, Biology and Life Sciences, Proteins, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Antibodies, Neutralizing, 030104 developmental biology, lcsh:Biology (General), Amniotes, biology.protein, Parasitology, lcsh:RC581-607, Retroviridae Infections
Abstract

Human diseases of zoonotic origin are a major public health problem. Simian foamy viruses (SFVs) are complex retroviruses which are currently spilling over to humans. Replication-competent SFVs persist over the lifetime of their human hosts, without spreading to secondary hosts, suggesting the presence of efficient immune control. Accordingly, we aimed to perform an in-depth characterization of neutralizing antibodies raised by humans infected with a zoonotic SFV. We quantified the neutralizing capacity of plasma samples from 58 SFV-infected hunters against primary zoonotic gorilla and chimpanzee SFV strains, and laboratory-adapted chimpanzee SFV. The genotype of the strain infecting each hunter was identified by direct sequencing of the env gene amplified from the buffy coat with genotype-specific primers. Foamy virus vector particles (FVV) enveloped by wild-type and chimeric gorilla SFV were used to map the envelope region targeted by antibodies. Here, we showed high titers of neutralizing antibodies in the plasma of most SFV-infected individuals. Neutralizing antibodies target the dimorphic portion of the envelope protein surface domain. Epitopes recognized by neutralizing antibodies have been conserved during the cospeciation of SFV with their nonhuman primate host. Greater neutralization breadth in plasma samples of SFV-infected humans was statistically associated with smaller SFV-related hematological changes. The neutralization patterns provide evidence for persistent expression of viral proteins and a high prevalence of coinfection. In conclusion, neutralizing antibodies raised against zoonotic SFV target immunodominant and conserved epitopes located in the receptor binding domain. These properties support their potential role in restricting the spread of SFV in the human population., Author summary Foamy viruses are the oldest known retroviruses and have been mostly described to be nonpathogenic in their natural animal hosts. Simian foamy viruses (SFVs) can be transmitted to humans, in whom they establish persistent infection, as have the simian lenti- and deltaviruses that led to the emergence of two major human pathogens, human immunodeficiency virus type 1 (HIV-1) and human T lymphotropic virus type 1 (HTLV-1). Such cross-species transmission of SFV is ongoing in many parts of the world where humans have contact with nonhuman primates. We present the first comprehensive study of neutralizing antibodies in SFV-infected humans. We showed high titers of neutralizing antibodies in the plasma of most SFV-infected individuals. Neutralizing antibodies target the dimorphic portion of the envelope protein surface domain that overlap with the receptor binding domain. SFV-specific antibodies target epitopes conserved over 8 million years of co-speciation with their nonhuman primate host. Greater neutralization potency in infected individuals was statistically associated with smaller SFV-related hematological changes. In conclusion, our results suggest the protective action of neutralizing antibodies against SFV infection and spread in the human population.

Published
2018

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