HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation.
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.
Chomont
Nicolas
N
Laboratoire d'Immunologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal Saint-Luc, Montréal, Québec, Canada.
El-Far
Mohamed
M
Ancuta
Petronela
P
Trautmann
Lydie
L
Procopio
Francesco A
FA
Yassine-Diab
Bader
B
Boucher
Geneviève
G
Boulassel
Mohamed-Rachid
MR
Ghattas
Georges
G
Brenchley
Jason M
JM
Schacker
Timothy W
TW
Hill
Brenna J
BJ
Douek
Daniel C
DC
Routy
Jean-Pierre
JP
Haddad
Elias K
EK
Sékaly
Rafick-Pierre
RP
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
D019380:Anti-HIV Agents