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Cell Rep. 2012 Oct 25;2(4):807-16. doi: 10.1016/j.celrep.2012.09.008. Epub 2012 Oct 4.

Reactivation of latent HIV-1 by inhibition of BRD4.

Author information

1
Department of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02127, USA.

Abstract

HIV-1 depends on many host factors for propagation. Other host factors, however, antagonize HIV-1 and may have profound effects on viral activation. Curing HIV-1 requires the reduction of latent viral reservoirs that remain in the face of antiretroviral therapy. Using orthologous genetic screens, we identified bromodomain containing 4 (BRD4) as a negative regulator of HIV-1 replication. Antagonism of BRD4, via RNA interference or with a small molecule inhibitor, JQ1, both increased proviral transcriptional elongation and alleviated HIV-1 latency in cell-line models. In multiple instances, JQ1, when used in combination with the NF-κB activators Prostratin or PHA, enhanced the in vitro reactivation of latent HIV-1 in primary T cells. These data are consistent with a model wherein BRD4 competes with the virus for HIV-1 dependency factors (HDFs) and suggests that combinatorial therapies that activate HDFs and antagonize HIV-1 competitive factors may be useful for curing HIV-1 infection.

PMID:
23041316
PMCID:
PMC3523124
DOI:
10.1016/j.celrep.2012.09.008
[Indexed for MEDLINE]
Free PMC Article

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