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2 results on '"Virus et Immunité - Virus and immunity"'

1. Interplay between SARS-CoV-2 and the type I interferon response

Author

Marlène Dreux, Margarida Sa Ribero, Nolwenn Jouvenet, Sébastien Nisole, Trafic Vésiculaire, Réponse Innée et Virus – Vesicular trafficking, Innate response, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Research in the laboratory of NJ is funded by the CNRS, the Institut Pasteur, the European Molecular Biology Organisation (EMBO) Young Investigator Program, and the Agence Nationale de la Recherche Scientifique (ANR 16 CE15 0025 01 VIRO-STORM). Research related to the topic of this review in the team led by MD is supported by the Agence Nationale de la Recherche (ANR Flash COVID-19 and ANR 19-CE15-0025-01 JCJC iSYN). Research related to the topic of this review in the team led by SN is supported by the Labex EpiGenMed, an Investissements d’avenir program (ANR-10-LABX-12-01), the Région Occitanie and the Agence Nationale de la Recherche (ANR Flash COVID-19)., ANR-16-CE15-0025,Viro-Storm,Mécanismes de production incontrôlée de cytokines au cours de l'infection virale(2016), ANR-10-LABX-0012,EpiGenMed,From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Bodescot, Myriam, Mécanismes de production incontrôlée de cytokines au cours de l'infection virale - - Viro-Storm2016 - ANR-16-CE15-0025 - AAPG2016 - VALID, Laboratoires d'excellence - From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow - - EpiGenMed2010 - ANR-10-LABX-0012 - LABX - VALID, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Virus et Immunité - Virus and immunity (CNRS-UMR3569)

Subjects
RNA viruses, Viral Diseases, Pulmonology, Coronaviruses, viruses, Disease, Review, medicine.disease_cause, Biochemistry, Medical Conditions, Interferon, Biology (General), Pathology and laboratory medicine, Coronavirus, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 030302 biochemistry & molecular biology, virus diseases, Medical microbiology, Prognosis, 3. Good health, STAT proteins, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, Interferon Type I, [SDV.IMM]Life Sciences [q-bio]/Immunology, SARS CoV 2, Pathogens, Coronavirus Infections, COVID-19, Respiratory infections, Interferons, SARS coronavirus, Viral replication, SARS-CoV-2, STAT protein, medicine.drug, [SDV.IMM] Life Sciences [q-bio]/Immunology, QH301-705.5, Immunology, Pneumonia, Viral, Biology, Microbiology, Antiviral Agents, Proinflammatory cytokine, 03 medical and health sciences, Respiratory Disorders, Betacoronavirus, Immune system, Immunity, Virology, Genetics, medicine, Humans, Molecular Biology, Pandemics, 030304 developmental biology, Medicine and health sciences, Biology and life sciences, Organisms, Viral pathogens, Proteins, Covid 19, Dendritic Cells, RC581-607, Viral Replication, Immunity, Innate, respiratory tract diseases, Microbial pathogens, COVID-19 Drug Treatment, Respiratory Infections, Parasitology, Immunologic diseases. Allergy
Abstract

International audience; The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. An unbalanced immune response, characterized by a weak production of type I interferons (IFN-Is) and an exacerbated release of proinflammatory cytokines, contributes to the severe forms of the disease. SARS-CoV-2 is genetically related to SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV), which caused outbreaks in 2003 and 2013, respectively. Although IFN treatment gave some encouraging results against SARS-CoV and MERS-CoV in animal models, its potential as a therapeutic against COVID-19 awaits validation. Here, we describe our current knowledge of the complex interplay between SARS-CoV-2 infection and the IFN system, highlighting some of the gaps that need to be filled for a better understanding of the underlying molecular mechanisms. In addition to the conserved IFN evasion strategies that are likely shared with SARS-CoV and MERS-CoV, novel counteraction mechanisms are being discovered in SARS-CoV-2-infected cells. Since the last coronavirus epidemic, we have made considerable progress in understanding the IFN-I response, including its spatiotemporal regulation and the prominent role of plasmacytoid dendritic cells (pDCs), which are the main IFN-I-producing cells. While awaiting the results of the many clinical trials that are evaluating the efficacy of IFN-I alone or in combination with antiviral molecules, we discuss the potential benefits of a well-timed IFN-I treatment and propose strategies to boost pDC-mediated IFN responses during the early stages of viral infection.

Published
2020
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2. 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
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