HIV Tat/P-TEFb Interaction: A Potential Target for Novel Anti-HIV Therapies.

HIV Tat/P-TEFb Interaction: A Potential Target for Novel Anti-HIV Therapies.
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DOI:
10.3390/molecules23040933
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发表时间:
2018-04-17
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Okamoto T
Okamoto T
中科院分区:
其他
文献类型:
--
作者:
Asamitsu K;Fujinaga K;Okamoto T

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转录是人类免疫缺陷病毒1型(HIV 1)生命周期中的关键步骤,主要参与维持病毒潜伏期。病毒和细胞转录因子,包括转录激活因子、抑制蛋白和表观遗传因子,都参与HIV从宿主细胞基因组内整合的前病毒DNA转录。其中,病毒编码的转录激活因子Tat是HIV转录的主要调控因子。有趣的是,与其他已知的转录激活因子不同,Tat主要通过与细胞正转录延伸因子b (P-TEFb)相互作用来激活转录延伸和起始。在这篇综述中,我们描述了Tat如何通过与P-TEFb的相互作用激活病毒转录的分子机制。我们提出了一种通过阻断Tat作用来对抗HIV复制的新治疗策略。
Transcription is a crucial step in the life cycle of the human immunodeficiency virus type 1 (HIV 1) and is primarily involved in the maintenance of viral latency. Both viral and cellular transcription factors, including transcriptional activators, suppressor proteins and epigenetic factors, are involved in HIV transcription from the proviral DNA integrated within the host cell genome. Among them, the virus-encoded transcriptional activator Tat is the master regulator of HIV transcription. Interestingly, unlike other known transcriptional activators, Tat primarily activates transcriptional elongation and initiation by interacting with the cellular positive transcriptional elongation factor b (P-TEFb). In this review, we describe the molecular mechanism underlying how Tat activates viral transcription through interaction with P-TEFb. We propose a novel therapeutic strategy against HIV replication through blocking Tat action.
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