Proliferative memory SAMHD1low CD4+ T cells harbour high levels of HIV-1 with compartmentalized viral populations
| العنوان: | Proliferative memory SAMHD1low CD4+ T cells harbour high levels of HIV-1 with compartmentalized viral populations |
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| المؤلفون: | 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 |
| المساهمون: | 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), Virus et Immunité - Virus and immunity (CNRS-UMR3569) |
| المصدر: | PLoS Pathogens PLoS Pathogens, Public Library of Science, 2019, 15 (6), pp.e1007868. ⟨10.1371/journal.ppat.1007868⟩ PLoS Pathogens, 2019, 15 (6), pp.e1007868. ⟨10.1371/journal.ppat.1007868⟩ PLoS Pathogens, Vol 15, Iss 6, p e1007868 (2019) |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1553-7374 1553-7366 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1e14475c51610b8414d906bf964631f2Test https://pubmed.ncbi.nlm.nih.gov/31220191Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1e14475c51610b8414d906bf964631f2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 15537366 |
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