Inhibition of the HIV Rev transactivator : a new target for therapeutic intervention.
Inhibition of the HIV Rev transactivator : a new target for therapeutic intervention.
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DOI：
10.2741/a191
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发表时间：
1997-06
期刊：
影响因子：
--
通讯作者：
A. Heguy
中科院分区：
文献类型：
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作者：
A. Heguy
病毒反式激活因子REV对HIV复制是必不可少的，因为它允许编码结构蛋白的未剪接和部分剪接的病毒mRNAs的核输出。REV是一种RNA结合蛋白，它与在包膜序列中发现的高度结构的RNA元件RRE相互作用。这种病毒蛋白还与称为核孔蛋白的细胞蛋白相互作用，并作为病毒mRNAs和细胞核输出机制之间的适配器。这两种交互都是特定的，并且是REV功能所必需的。由于其在HIV复制周期中的关键作用和其新颖的作用机制，REV是治疗干预的理想靶点。本文对REV抑制的研究进展作一综述。将讨论基因治疗方法，包括反式显性突变体和RNA诱骗的表达，以及REV-RRE结合或REV与细胞器相互作用的反义治疗和小分子抑制剂
The viral transactivator Rev is essential for HIV replication, since it allows the nuclear export of unspliced and partially spliced viral mRNAs that encode the structural proteins. Rev is an RNA binding protein that interacts with a highly structured RNA element, the RRE, found within the envelope sequences. This viral protein also interacts with cellular proteins, termed nucleoporins, and acts as an adaptor between the viral mRNAs and the cellular nuclear export machinery. Both interactions are specific, and required for Rev function. Because of its crucial role in the HIV replication cycle, and its novel mechanism of action, Rev represents an ideal target for therapeutic intervention. This review describes the efforts towards Rev inhibition. Gene therapy approaches, including the expression of trans-dominant mutants and RNA decoys, as well as antisense therapies and small molecule inhibitors of Rev-RRE binding or Rev interaction with the cellular machinery will be discussed