A single HIV-1 cluster and a skewed immune homeostasis drive the early spread of HIV among resting CD4+ cell subsets within one month post-infection

Autor: Yazdan Yazdanpanah, Thierry Allegre, Adeline Mélard, Laurence Slama, Charline Bacchus, Bao Chau Phung Seksik, Brigitte Autran, Claudine Duvivier, Anne Leplatois, Clotilde Allavena, Christine Rouzioux, Laurence Meyer, Georges Nembot, Véronique Avettand-Fenoel, Jean-Michel Molina, Christine Katlama, Caroline Lascoux-Combe, Antoine Cheret, Catherine Blanc, Cécile Goujard
Přispěvatelé: Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Gustave Dron, Laboratoire de Virologie [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), 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), Plateforme Cytométrie Pitié-Salpêtrière (LUMIC-CYPS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Unité Mixte de Service d'Imagerie et de Cytométrie (UMS LUMIC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier du Pays d'Aix, Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Médecine interne-Immunologie clinique [Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital l'Archet, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Necker - Enfants Malades [AP-HP], INSERM U1018, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des maladies infectieuses et tropicales [CHU Tenon], 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 Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], 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 Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Plateforme Cytométrie Pitié-Salpêtrière ( CyPS ), Unité Mixte de Service d'Imagerie et de Cytométrie ( UMS LUMIC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des Maladies Infectieuses et Tropicales [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Université de Nantes ( UN ) -Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service des maladies infectieuses [CHU Pitié-Salêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], HAL UPMC, Gestionnaire, Service de Maladies infectieuses et tropicales [CHU Tenon], Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière]
Jazyk: angličtina
Rok vydání: 2013
Předmět:
CD4-Positive T-Lymphocytes
Male
Time Factors
lcsh:Medicine
HIV Infections
[ SDV.IMM.IA ] Life Sciences [q-bio]/Immunology/Adaptive immunology
0302 clinical medicine
Immunodeficiency Viruses
T-Lymphocyte Subsets
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Molecular Cell Biology
Blood plasma
Homeostasis
030212 general & internal medicine
lcsh:Science
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology
0303 health sciences
Multidisciplinary
T Cells
Middle Aged
Viral Load
Flow Cytometry
Viral Persistence and Latency
3. Good health
Host-Pathogen Interaction
[ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology
[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
Cytokines
Medicine
Infectious diseases
Female
Viral load
Research Article
Adult
Cell signaling
Immune Cells
Immunology
Retrovirology and HIV immunopathogenesis
Immunopathology
Viral diseases
Biology
Microbiology
[ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Viral Evolution
Virus
Immune Activation
Young Adult
03 medical and health sciences
Immune system
Virology
Humans
030304 developmental biology
lcsh:R
Immunity
HIV
In vitro
Immune System
DNA
Viral
HIV-1
lcsh:Q
Million Cells
Cytometry
Zdroj: PLoS ONE, Vol 8, Iss 5, p e64219 (2013)
PLoS ONE
PLoS ONE, 2013, 8 (5), pp.e64219. ⟨10.1371/journal.pone.0064219⟩
PLoS ONE, Public Library of Science, 2013, 8 (5), pp.e64219. ⟨10.1371/journal.pone.0064219⟩
PLoS ONE, Public Library of Science, 2013, 8 (5), pp.e64219. 〈10.1371/journal.pone.0064219〉
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0064219⟩
Popis: for the OPTIPRIM ANRS 147 study group; International audience; Optimizing therapeutic strategies for an HIV cure requires better understanding the characteristics of early HIV-1 spread among resting CD4+ cells within the first month of primary HIV-1 infection (PHI). We studied the immune distribution, diversity, and inducibility of total HIV-DNA among the following cell subsets: monocytes, peripheral blood activated and resting CD4 T cells, long-lived (naive [TN] and central-memory [TCM]) and short-lived (transitional-memory [TTM] and effector-memory cells [TEM]) resting CD4+T cells from 12 acutely-infected individuals recruited at a median 36 days from infection. Cells were sorted for total HIV-DNA quantification, phylogenetic analysis and inducibility, all studied in relation to activation status and cell signaling. One month post-infection, a single CCR5-restricted viral cluster was massively distributed in all resting CD4+ subsets from 88% subjects, while one subject showed a slight diversity. High levels of total HIV-DNA were measured among TN (median 3.4 log copies/million cells), although 10-foldless (p = 0.0005) than inequally infected TCM (4.5), TTM (4.7) and TEM(4.6) cells. CD32CD4+ monocytes harbored a low viral burden (median 2.3 log copies/million cells), unlike equally infected resting and activated CD4+ T cells (4.5 log copies/million cells). The skewed repartition of resting CD4 subsets influenced their contribution to the pool of resting infected CD4+T cells, two thirds of which consisted of short-lived TTM and TEM subsets, whereas long-lived TN and TCM subsets contributed the balance. Each resting CD4 subset produced HIV in vitro after stimulation with anti-CD3/anti-CD28+IL-2 with kinetics and magnitude varying according to subset differentiation, while IL-7 preferentially induced virus production from long-lived resting TN cells. In conclusion, within a month of infection, a clonal HIV-1 cluster is massively distributed among resting CD4 T-cell subsets with a flexible inducibility, suggesting that subset activation and skewed immune homeostasis determine the conditions of viral dissemination and early establishment of the HIV reservoir.
Databáze: OpenAIRE
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