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

• Published in: PloS one Vol. 8; no. 5; p. e64219
• Main Authors: Bacchus, Charline, Cheret, Antoine, Avettand-Fenoël, Véronique, Nembot, Georges, Mélard, Adeline, Blanc, Catherine, Lascoux-Combe, Caroline, Slama, Laurence, Allegre, Thierry, Allavena, Clotilde, Yazdanpanah, Yazdan, Duvivier, Claudine, Katlama, Christine, Goujard, Cécile, Seksik, Bao Chau Phung, Leplatois, Anne, Molina, Jean-Michel, Meyer, Laurence, Autran, Brigitte, Rouzioux, Christine
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.05.2013; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adaptive immunology; Adult; AIDS; Analysis; Biology; CCR5 protein; CD28 antigen; CD3 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cell activation; Clusters; Computer memory; Cytokines; Deoxyribonucleic acid; DNA; DNA, Viral - metabolism; Effector cells; Epidemiology; Female; Health aspects; HIV; HIV Infections - immunology; HIV Infections - virology; HIV-1 - physiology; Homeostasis; Homeostasis - immunology; Hospitals; Human health and pathology; Human immunodeficiency virus; Humans; Immunology; Infection; Infections; Infectious diseases; Interleukin 2; Interleukin 7; Kinetics; Laboratories; Life Sciences; Lymphocytes; Lymphocytes T; Male; Medical research; Medicine; Memory cells; Microbiology and Parasitology; Middle Aged; Monocytes; Peripheral blood; Phylogeny; Public health; Signaling; T cells; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - virology; Time Factors; Viral Load - immunology; Virology; Viruses; Young Adult; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0064219

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-fold less (p = 0.0005) than in equally infected TCM (4.5), TTM (4.7) and TEM (4.6) cells. CD3-CD4+ 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.