Author/Editor     Contreras, Xavier; Schweneker, Marc; Chen, Ching-Shih; McCune, Joseph M; Deeks, Steven G; Martin, Jeffrey; Peterlin, Matija B
Title     Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells
Type     članek
Source     J Biol Chem
Vol. and No.     Letnik 284, št. 11
Publication year     2009
Volume     str. 6782-9
Language     eng
Abstract     Human immunodeficiency virus (HIV) persists in a latent form in infected individuals treated effectively with highly active antiretroviral therapy (HAART). In part, these latent proviruses account for the rebound in viral replication observed after treatment interruption. A major therapeutic challenge is to purge this reservoir. In this study, we demonstrate that suberoylanilide hydroxamic acid (SAHA) reactivates HIV from latency in chronically infected cell lines and primary cells. Indeed, P-TEFb, a critical transcription cofactor for HIV, is released and then recruited to the viral promoter upon stimulation with SAHA. The phosphatidylinositol 3-kinase/Akt pathway is involved in the initiation of these events. Using flow cytometry-based single cell analysis of protein phosphorylation, we demonstrate that SAHA activates this pathway in several subpopulations of T cells, including memory T cells that are the major viral reservoir in peripheral blood. Importantly, SAHA activates HIV replication in peripheral blood mononuclear cells from individuals treated effectively with HAART. Thus SAHA, which is a Food and Drug Administration-approved drug, might be considered to accelerate the decay of the latent reservoir in HAART-treated infected humans.
Descriptors     ADULT
HIV
HIV INFECTIONS
HYDROXAMIC ACIDS
IMMUNOLOGIC MEMORY
JURKAT CELLS
PROVIRUSES
T-LYMPHOCYTES
VIRUS LATENCY
VIRUS REPLICATION