title: 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.
abstract: 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.
authors.affiliation: Pierre-and-Marie-Curie University Paris 06, Laboratory Immunity and Infection UMR_S 945, F-75013, Paris, France.
authors.forename: Charline
authors.initials: C
authors.lastname: Bacchus
authors.forename: Antoine
authors.initials: A
authors.lastname: Cheret
authors.forename: Véronique
authors.initials: V
authors.lastname: Avettand-Fenoël
authors.forename: Georges
authors.initials: G
authors.lastname: Nembot
authors.forename: Adeline
authors.initials: A
authors.lastname: Mélard
authors.forename: Catherine
authors.initials: C
authors.lastname: Blanc
authors.forename: Caroline
authors.initials: C
authors.lastname: Lascoux-Combe
authors.forename: Laurence
authors.initials: L
authors.lastname: Slama
authors.forename: Thierry
authors.initials: T
authors.lastname: Allegre
authors.forename: Clotilde
authors.initials: C
authors.lastname: Allavena
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Yazdanpanah
authors.forename: Claudine
authors.initials: C
authors.lastname: Duvivier
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
authors.forename: Bao Chau Phung
authors.initials: BC
authors.lastname: Seksik
authors.forename: Anne
authors.initials: A
authors.lastname: Leplatois
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology*; D013997:Time Factors; D019562:Viral Load / Q000276:immunology; D055815:Young Adult
chemical_list: D004279:DNA, Viral