β-TrCP Dependency of HIV-1 Vpu-Induced Downregulation of CD4 and BST-2/Tetherin
β-TrCP Dependency of HIV-1 Vpu-Induced Downregulation of CD4 and BST-2/Tetherin
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DOI：
10.2174/157016212800792441
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发表时间：
2012-06-01
影响因子：
1
通讯作者：
Piguet, Vincent
中科院分区：
文献类型：
--
作者：
Blanchet, Fabien P.;Mitchell, J. P.;Piguet, Vincent
在进化过程中，病原体已经进化出对抗关键细胞限制机制的策略，以便有效地侵入靶细胞并完成其复制周期的重要步骤。人类免疫缺陷病毒-1和一些猿猴对应物表达一种影响病毒复制的小的多功能蛋白Vpu。通过充当多功能适配器，Vpu增强病毒颗粒释放和感染性。因此，Vpu，一种辅助蛋白，有助于发病机制，同时避免重复感染。这些作用主要依赖于Vpu靶向宿主蛋白CD 4和BST-2/tetherin的能力。事实上，Vpu下调这些受体的细胞表面表达，随后通过涉及含β-TrCP的E3泛素连接酶复合物的机制诱导其蛋白水解。在这篇综述中，我们将详细介绍最近的研究，旨在阐明Vpu介导的CD 4和BST-2/tetherin下调和降解的机制，以及它们对病毒发病机制的后续后果。
During evolution, pathogens have evolved strategies to counteract key cellular restriction mechanisms in order to efficiently invade target cells and fulfill essential steps of their replication cycle. Human Immunodeficiency Virus-1 and some Simian counterparts express a small multifunctional protein, Vpu, which influences viral replication. By acting as a multifunctional adapter, Vpu enhances viral particle release and infectivity. Therefore Vpu, an accessory protein, contributes to pathogenesis while avoiding superinfection. These effects rely mainly on the ability of Vpu to target the host proteins CD4 and BST-2/tetherin. Indeed, Vpu downregulates the cell surface expression of these receptors and subsequently induces their proteolysis via a mechanism involving a beta-TrCP-containing E3 ubiquitin ligase complex. In this review, we will detail recent research aimed at elucidating the mechanism of Vpu-mediated CD4 and BST-2/tetherin downregulation and degradation as well as their subsequent consequences on viral pathogenesis.