Histone deacetylase inhibitors (HDACis) that release the positive transcription elongation factor b (P-TEFb) from its inhibitory complex also activate HIV transcription
Bartholomeeusen, Koen ...
Numerous studies have looked at effects of histone deacetylase inhibitors (HDACis) on HIV reactivation in established transformed cell lines and primary CD4+ T cells. However, their findings remain ...confusing and differences between effects of class I- and class II-specific HDACis persist. Since no clear picture emerged, we decided to determine how HDACis reactivate HIV in transformed cell lines and primary cells. We found that neither histone H3 nor tubulin acetylation correlated with HIV reactivation in Jurkat and HeLa cells. Rather, HDACis that could reactivate HIV in chromatin or on episomal plasmids, also released free P-TEFb from its inhibitory 7SK snRNP. In resting primary CD4+ T cells, where levels of P-TEFb are vanishingly low, the most potent HDACi, SAHA, had minimal effects. In contrast, when these cells were treated with a PKC agonist, Bryostatin 1, which increased levels of P-TEFb, then SAHA once again reactivated HIV. We conclude that HDACis, which can reactivate HIV, work via the release of free P-TEFb from the 7SK snRNP.
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