Budhiraja Sona, Rice Andrew P
Department of Molecular Microbiology & Virology, Baylor College of Medicine, Houston, TX 77030, USA.
Future Virol. 2013 Jul 1;8(7). doi: 10.2217/fvl.13.52.
The HIV/AIDS field is gaining momentum in the goal of finding a functional cure for HIV infection by utilizing strategies that specifically reactivate the latent viral reservoir in combination with the HAART regimen to prevent further viral spread. Small-molecule inhibitors such as histone deacetylase (HDAC) and bromodomain and extraterminal (BET) inhibitors can successfully activate HIV transcription and reverse viral latency in clonal cell lines. However, in resting CD4 T cells, thought to be the principal physiological reservoir of latent HIV, their effect in reactivating the viral reservoir is more variable. It is possible that the discrepant responsiveness of quiescent primary CD4 T cells to HDAC and BET inhibitors could be attributed to the limiting levels of P-TEFb, a key viral transcription host cofactor, in these cells. In this review, we discuss the role of P-TEFb and the necessity for its mobilization in stimulating viral reactivation from latency upon treatment with HDAC and BET inhibitors.
通过采用特定策略重新激活潜伏病毒库并结合高效抗逆转录病毒治疗（HAART）方案以防止病毒进一步传播，在寻找HIV感染功能性治愈方法的目标上，HIV/AIDS领域正不断取得进展。诸如组蛋白去乙酰化酶（HDAC）和溴结构域及额外末端（BET）抑制剂等小分子抑制剂能够成功激活HIV转录并逆转克隆细胞系中的病毒潜伏状态。然而，在被认为是潜伏HIV主要生理储存库的静息CD4 T细胞中，它们在重新激活病毒库方面的效果更具变数。静止原代CD4 T细胞对HDAC和BET抑制剂反应不一致，可能是由于这些细胞中关键的病毒转录宿主辅因子P-TEFb水平有限。在本综述中，我们讨论了P-TEFb的作用以及在用HDAC和BET抑制剂治疗时其动员对于刺激病毒从潜伏状态重新激活的必要性。
