Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106; email:
Annu Rev Virol. 2017 Sep 29;4(1):261-285. doi: 10.1146/annurev-virology-101416-041646. Epub 2017 Jul 17.
Although potent combination antiretroviral therapy can effectively block viral replication in the host, human immunodeficiency virus (HIV) persists due to the existence of latent but replication-competent proviruses residing primarily in a very small population of resting memory CD4 T cells. Viral latency is established when the expression of the autoregulatory viral trans-activating factor Tat is reduced to subthreshold levels. The absence of Tat reduces HIV transcription and protein production to levels that make the host cell invisible to the immune system and refractory to antiretroviral treatment. Key host cell mechanisms that drive HIV into latency are sequestration of transcription initiation factors, establishment of epigenetic barriers inactivating the proviral promoter, and blockage of the assembly of the host elongation factor P-TEFb. This comprehensive understanding of the molecular control of HIV transcription is leading to the development of optimized combinatorial reactivation and immune surveillance strategies designed to purge the latent viral reservoir.
尽管强效联合抗逆转录病毒疗法可以有效地阻止宿主中的病毒复制，但由于潜伏但具有复制能力的前病毒主要存在于极少数静止记忆 CD4 T 细胞中，人类免疫缺陷病毒 (HIV) 仍然存在。当自身调节病毒反式激活因子 Tat 的表达降低到亚阈值水平时，病毒潜伏期就会建立。Tat 的缺乏会降低 HIV 的转录和蛋白产生水平，使宿主细胞对免疫系统不可见，并对抗逆转录病毒治疗产生抗性。驱使 HIV 进入潜伏期的关键宿主细胞机制包括转录起始因子的隔离、前病毒启动子的表观遗传障碍的建立，以及阻止宿主延伸因子 P-TEFb 的组装。对 HIV 转录的分子控制的全面理解，正在导致开发优化的组合再激活和免疫监测策略，旨在清除潜伏的病毒库。
