Journal of Zhejiang University

Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.5 P.455-465

Mechanism and factors that control HIV-1 transcription and latency activation*

Author(s): Rong-diao Liu,Jun Wu,Rui Shao,Yu-hua Xue
Affiliation(s): 1. . School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China
Corresponding email(s): xueyuhua@xmu.edu.cn
Key Words: HIV-1, Transcriptional elongation, RNA polymerase II, Tat, P-TEFb

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Rong-diao Liu, Jun Wu, Rui Shao, Yu-hua Xue. Mechanism and factors that control HIV-1 transcription and latency activation[J]. Journal of Zhejiang University Science B, 2014, 15(5): 455-465.

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author="Rong-diao Liu, Jun Wu, Rui Shao, Yu-hua Xue",
journal="Journal of Zhejiang University Science B",
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number="5",
pages="455-465",
year="2014",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1400059"
}

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%DOI 10.1631/jzus.B1400059

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T1 - Mechanism and factors that control HIV-1 transcription and latency activation
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SP - 455
EP - 465
%@ 1673-1581
Y1 - 2014
PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1400059

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: After reverse transcription, the HIV-1 proviral DNA is integrated into the host genome and thus subjected to transcription by the host RNA polymerase II (Pol II). With the identification and characterization of human p-TEFb in the late 1990s as a specific host cofactor required for HIV-1 transcription, it is now believed that the elongation stage of Pol II transcription plays a particularly important role in regulating HIV-1 gene expression. HIV-1 uses a sophisticated scheme to recruit human p-TEFb and other cofactors to the viral long terminal repeat (LTR) to produce full-length HIV-1 transcripts. In this process, p-TEFb is regulated by the reversible association with various transcription factors/cofactors to form several multi-subunit complexes (e.g., 7SK snRNP, super elongation complexes (SECs), and the Brd4-p-TEFb complex) that collectively constitute a p-TEFb network for controlling cellular and HIV-1 transcription. Recent progresses in HIV-1 transcription were reviewed in the paper, with the emphasis on the mechanism and factors that control HIV-1 transcription and latency activation.

调控HIV-1转录和潜伏激活的机制及相关因子

本文概要：（1）反式激活蛋白（Tat）是病毒复制的重要因子，正性转录延伸因子b（P-TEFb）是Tat反式激活HIV-1转录所必需的特异性宿主细胞因子，其活性与HIV-1的转录密切相关。（2）在细胞内，无活性7SK snRNP复合体是功能性有活性P-TEFb的贮存和来源。在特定条件下，7SK snRNP复合体发生解离并释放出P-TEFb，从而刺激转录延伸。可以说，P-TEFb的活性受到严格的调控，维持着一种动态的平衡。（3）同时，P-TEFb还存在于一个具有超高转录活性的超级延伸复合体（SEC）中。Tat能将含有两个延伸因子P-TEFb和ELL2的SEC复合体募集至HIV-1长末端结构域（LTR），然后众多因子协同作用有效地增强HIV-1的转录作用。（4）溴区包含蛋白4（Brd4）像Tat一样，将P-TEFb募集至众多细胞基因的启动子区域，促进转录。Brd4也可激活基础水平的HIV-1转录，却对依赖Tat的HIV-1转录具有抑制作用，因为Brd4和Tat竞争性地与P-TEFb结合。（5）鉴于Brd4对Tat依赖性HIV-1转录的抑制作用，寻找能够抑制Brd4的小分子药物，激活HIV-1潜伏，结合高效抗逆转录病毒治疗（HAART），使得彻底根除HIV-1变成可能。Brd4的抑制剂JQ1就是这样的一种小分子，并且已被证明可以在多种细胞模型中激活HIV-1潜伏。

关键词：人类免疫缺陷病毒（HIV-1）；转录延伸；RNA聚合酶II；Tat；P-TEFb