title: HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation.
abstract: HIV persists in a reservoir of latently infected CD4(+) T cells in individuals treated with highly active antiretroviral therapy (HAART). Here we identify central memory (T(CM)) and transitional memory (T(TM)) CD4(+) T cells as the major cellular reservoirs for HIV and find that viral persistence is ensured by two different mechanisms. HIV primarily persists in T(CM) cells in subjects showing reconstitution of the CD4(+) compartment upon HAART. This reservoir is maintained through T cell survival and low-level antigen-driven proliferation and is slowly depleted with time. In contrast, proviral DNA is preferentially detected in T(TM) cells from aviremic individuals with low CD4(+) counts and higher amounts of interleukin-7-mediated homeostatic proliferation, a mechanism that ensures the persistence of these cells. Our results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and, as in cancer, drugs that interfere with the self renewal and persistence of proliferating memory T cells.
authors: Laboratoire d'Immunologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal Saint-Luc, Montréal, Québec, Canada.
authors: Nicolas
authors: N
authors: Chomont
authors: Mohamed
authors: M
authors: El-Far
authors: Petronela
authors: P
authors: Ancuta
authors: Lydie
authors: L
authors: Trautmann
authors: Francesco A
authors: FA
authors: Procopio
authors: Bader
authors: B
authors: Yassine-Diab
authors: Geneviève
authors: G
authors: Boucher
authors: Mohamed-Rachid
authors: MR
authors: Boulassel
authors: Georges
authors: G
authors: Ghattas
authors: Jason M
authors: JM
authors: Brenchley
authors: Timothy W
authors: TW
authors: Schacker
authors: Brenna J
authors: BJ
authors: Hill
authors: Daniel C
authors: DC
authors: Douek
authors: Jean-Pierre
authors: JP
authors: Routy
authors: Elias K
authors: EK
authors: Haddad
authors: Rafick-Pierre
authors: RP
authors: Sékaly
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D049109:Cell Proliferation; D002470:Cell Survival; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D019562:Viral Load; D017735:Virus Latency / Q000276:immunology*; D014779:Virus Replication / Q000502:physiology
chemical_list: D019380:Anti-HIV Agents