The Tat Inhibitor Didehydro-Cortistatin A Prevents HIV-1 Reactivation from Latency.

ABSTRACT:

Unlabelled

Antiretroviral therapy (ART) inhibits HIV-1 replication, but the virus persists in latently infected resting memory CD4(+) T cells susceptible to viral reactivation. The virus-encoded early gene product Tat activates transcription of the viral genome and promotes exponential viral production. Here we show that the Tat inhibitor didehydro-cortistatin A (dCA), unlike other antiretrovirals, reduces residual levels of viral transcription in several models of HIV latency, breaks the Tat-mediated transcriptional feedback loop, and establishes a nearly permanent state of latency, which greatly diminishes the capacity for virus reactivation. Importantly, treatment with dCA induces inactivation of viral transcription even after its removal, suggesting that the HIV promoter is epi

SUBMITTER: Mousseau G 

PROVIDER: S-EPMC4495168 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature