ReferenceID 3524
Reactivation of latent HIV-1 by inhibition of BRD4
Cell Rep
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 r
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Record Fields
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- Reference Id
- 3524
- Evidence Id
- 20114
- Core Evidence Id
- 20114
- Source Reference Id
- 352
- Herb2 Reference Id
- HBREF000643
- Subject Paper Key
- HBIN040889_23041316
- Pubmed Id
- 23041316
- Doi
- 10.1016/j.celrep.2012.09.008
- Paper Title
- Reactivation of latent HIV-1 by inhibition of BRD4
- Paper 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.
- Journal
- Cell Rep
- Publish Year
- 2012
- Experiment Subject
- j-lat cell line, human cd4 t cell
- Experiment Type
- Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Reactivation of latent HIV-1 by inhibition of BRD4
- Bilingual Status
- semi_complete