Inhibitory effect of human TRIM5α on HIV-1 production
Inhibitory effect of human TRIM5α on HIV-1 production
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DOI：
10.1016/j.micinf.2010.05.004
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发表时间：
2010-09-01
影响因子：
5.8
通讯作者：
Shida, Hisatoshi
中科院分区：
文献类型：
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作者：
Zhang, Xianfeng;Kondo, Mariko;Shida, Hisatoshi
含有三分基序的5异构体-α（TRIM 5 α）是一种宿主限制因子，其以物种特异性方式在进入后、整合前阶段阻断一些逆转录病毒的感染。Sakuma等人最近的一份报告描述了恒河猴TRIM 5 α的第二种抗逆转录病毒活性，该活性通过快速降解HIV-1 Gag多聚蛋白来阻断HIV-1的产生。在这里，我们发现人类TRIM 5 α限制了HIV-1的产生。TRIM 5 α的瞬时表达降低了HIV-1的产生，而在人类细胞中TRIM 5 α的敲低增加了病毒体的释放。SPRY结构域中的单个氨基酸取代（R437 C）减弱了限制作用。中等水平的人野生型TRIM 5 α和少量的R437 C突变体掺入HIV-1病毒粒子中。R437 C突变体也失去了对N-嗜性小鼠白血病病毒感染的限制活性。然而，恒河猴TRIM 5 α中相应的R到C突变对限制能力没有影响。我们的研究结果表明，人TRIM 5 α是一种抗HIV-1感染的内在免疫因子。SPRY结构域第437位精氨酸对晚期限制的重要性具有种属特异性。(C)2010年Elsevier Masson SAS。All rights reserved.
Tripartite motif-containing 5 isoform-alpha (TRIM5 alpha), a host restriction factor, blocks infection of some retroviruses at a post-entry, pre-integration stage in a species-specific manner. A recent report by Sakuma et al. describes a second antiretroviral activity of rhesus macaque TRIM5 alpha, which blocks HIV-1 production through rapid degradation of HIV-1 Gag polyproteins. Here, we find that human TRIM5 alpha limits HIV-1 production. Transient expression of TRIM5 alpha decreased HIV-1 production, whereas knockdown of TRIM5 alpha in human cells increased virion release. A single amino acid substitution (R437C) in the SPRY domain diminished the restriction effect. Moderate levels of human wild-type TRIM5 alpha and a little amount of R437C mutant were incorporated into HIV-1 virions. The R437C mutant also lost restriction activity against N-tropic murine leukemia virus infection. However, the corresponding R to C mutation in rhesus macaque TRIM5 alpha had no effect on the restriction ability. Our findings suggest human TRIM5 alpha is an intrinsic immunity factor against HIV-1 infection. The importance of arginine at 437 aa in SPRY domain for the late restriction is species-specific. (C) 2010 Elsevier Masson SAS. All rights reserved.