Avtor/Urednik		Contreras, Xavier; Schweneker, Marc; Chen, Ching-Shih; McCune, Joseph M; Deeks, Steven G; Martin, Jeffrey; Peterlin, Matija B
Naslov		Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells
Tip		članek
Vir		J Biol Chem
Vol. in št.		Letnik 284, št. 11
Leto izdaje		2009
Obseg		str. 6782-9
Jezik		eng
Abstrakt		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.
Deskriptorji		ADULT HIV HIV INFECTIONS HYDROXAMIC ACIDS IMMUNOLOGIC MEMORY JURKAT CELLS PROVIRUSES T-LYMPHOCYTES VIRUS LATENCY VIRUS REPLICATION