Anti-viral opportunities during transcriptional activation of latent HIV in the host chromatin.
Anti-viral opportunities during transcriptional activation of latent HIV in the host chromatin.
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DOI：
10.1016/j.ymeth.2010.09.001
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发表时间：
2011-01
期刊：
影响因子：
4.8
通讯作者：
Zhou, Ming-Ming
中科院分区：
文献类型：
--
作者：
Mujtaba, Shiraz;Zhou, Ming-Ming
人类免疫缺陷病毒（HIV）当整合到宿主染色体中时，以转录失活但有复制能力的状态存在。这种潜伏性感染是对HIV根除工作的一个重大挑战，因为存在于受感染细胞中的永久性病毒储库能够在免疫抑制时或在高活性抗逆转录病毒治疗中断期间使病毒载量激增。了解控制HIV前病毒潜伏期及其再激活的分子机制可以为宿主因素作为消除休眠HIV细胞库的治疗靶点提供新的视角。虽然HIV潜伏期的控制是多因素的，但已知染色质结构和染色质相关的转录机制是重要因素。例如，HIV前病毒的转录起始涉及染色质相关蛋白和病毒编码的反式激活因子达特之间复杂的分子相互作用。本文的第一部分讨论了我们目前对HIV转录激活和病毒mRNA延伸的理解，主要是HIV达特的翻译后修饰及其与宿主染色质修饰酶和染色质重塑复合物的相互作用。第二部分重点介绍了新的实验治疗方法，旨在管理HIV基因表达的激活剂，以减少或消除潜伏HIV感染的细胞池。
Human immunodeficiency virus (HIV) when integrated into a host chromosome exists in a transcriptionally inactive but replication-competent state. Such latent infection represents a major challenge to HIV eradication efforts because a permanent virus reservoir resided in the infected cell is able to spike the viral load on immune suppression or during interruption of highly active anti-retroviral therapy. Understanding the molecular mechanisms that control HIV proviral latency and its reactivation could provide new perspectives on host factors as therapeutic targets for abolishing cellular reservoirs of dormant HIV. Although the control of HIV latency is multifactorial, chromatin structure and the chromatin-associated transcriptional machinery are known to be important factors. For instance, transcription initiation of the HIV provirus involves a complex molecular interplay between chromatin-associated proteins and the virus-encoded trans-activator, Tat. The first part of this review discusses our current understanding of the elements involved in HIV transcriptional activation and viral mRNA elongation, mainly post-translational modifications of HIV Tat and its interactions with host chromatin-modifying enzymes and chromatin-remodeling complexes. The second part highlights new experimental therapeutic approaches aimed at administrating activators of HIV gene expression to reduce or eliminate the pool of latently HIV-infected cells.
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