TRIM5 and the Regulation of HIV-1 Infectivity.
TRIM5 and the Regulation of HIV-1 Infectivity.
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TRIM5 和 HIV-1 感染性的调节。
DOI：
10.1155/2012/426840
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Luban,Jeremy
中科院分区：
文献类型：
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作者：
Luban,Jeremy
过去十年，关于抑制HIV - 1和其他逆转录病毒复制的宿主限制因子的信息激增。TRIM5是这些因子之一，它是一种先天免疫信号分子，当逆转录病毒粒子核心被释放到易感靶细胞的细胞质中时，它就能识别衣壳晶格。衣壳晶格的识别有几个后果，包括TRIM5的多聚成互补晶格，病毒粒子核心的过早剥离，以及TRIM5 E3泛素连接酶活性的激活。产生无连接的K63连锁泛素链，激活TAK1激酶复合物和下游炎症介质。TRIM5衣壳识别结构域的多态性解释了在同源物中观察到的物种特异性差异以及人类TRIM5相对较弱的抗HIV - 1活性。更好地了解TRIM5和逆转录病毒衣壳晶格之间的复杂相互作用，可能有一天会导致利用这种相互作用开发有效的HIV‐1抑制剂。
The past ten years have seen an explosion of information concerning host restriction factors that inhibit the replication of HIV‐1 and other retroviruses. Among these factors is TRIM5, an innate immune signaling molecule that recognizes the capsid lattice as soon as the retrovirion core is released into the cytoplasm of otherwise susceptible target cells. Recognition of the capsid lattice has several consequences that include multimerization of TRIM5 into a complementary lattice, premature uncoating of the virion core, and activation of TRIM5 E3 ubiquitin ligase activity. Unattached, K63‐linked ubiquitin chains are generated that activate the TAK1 kinase complex and downstream inflammatory mediators. Polymorphisms in the capsid recognition domain of TRIM5 explain the observed species‐specific differences among orthologues and the relatively weak anti‐HIV‐1 activity of human TRIM5. Better understanding of the complex interaction between TRIM5 and the retrovirus capsid lattice may someday lead to exploitation of this interaction for the development of potent HIV‐1 inhibitors.