RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs
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RNA 解旋酶 MOV10 作为 HIV-1 Rev 的辅助因子,促进 Rev/RRE 依赖性病毒 mRNA 的核输出。

DOI:
10.1016/j.virol.2015.08.026
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发表时间:
2015-12-01
期刊:
影响因子:
3.7
通讯作者:
Zhang, Hui
Zhang, Hui
中科院分区:
医学3区
文献类型:
--
作者:
Huang, Feng;Zhang, Junsong;Zhang, Hui

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人类免疫缺陷病毒1型(HIV-1)在其复制过程中利用多种宿主因素。未剪接/部分剪接的病毒转录物的REV/RRE依赖性核输出需要宿主蛋白的帮助。最近的研究表明,MOV 10过表达抑制HIV-1复制的各个步骤。然而,内源性MOV 10在HIV-1复制的某些步骤中是必需的。在本报告中,我们发现MOV 10通过影响Rev/RRE轴,有效地增强病毒mRNA的核输出,随后增加Gag蛋白和其他晚期产物的表达。免疫共沉淀分析表明,MOV 10与Rev以RNA非依赖性方式相互作用。MOV 10的DEAG-box是增强Rev/RRE依赖的核输出所必需的,并且DEAG-box突变体显示出显性负活性。我们的数据表明,HIV-1利用抗病毒因子MOV 10作为Rev的辅助因子,并证明了MOV 10对HIV-1生命周期的复杂影响。(C)2015 Elsevier Inc. All rights reserved.
Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. (C) 2015 Elsevier Inc. All rights reserved.