The Vpu protein: new concepts in virus release and CD4 down-modulation.
The Vpu protein: new concepts in virus release and CD4 down-modulation.
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DOI：
10.2174/157016210791111124
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发表时间：
2010-04
影响因子：
1
通讯作者：
Stephens EB
中科院分区：
文献类型：
--
作者：
Ruiz A;Guatelli JC;Stephens EB
人类免疫缺陷病毒1型(HIV-1)和几种猴免疫缺陷病毒(SIV)编码一种称为VPU的跨膜蛋白。虽然它是HIV-1蛋白中最小的，但在病毒感染的细胞中有两个重要的功能。第一个功能是下调CD4受体，以阻止其与HIV-1包膜糖蛋白的相互作用。VPU与粗面内质网(RER)中的CD4受体相互作用，导致其跨粗面内质网(RER)重新移位，随后通过蛋白酶体途径降解。VPU蛋白的第二个主要功能是促进病毒从感染细胞中释放。先前的研究表明，病毒的释放是细胞类型特异性的，这表明某些细胞可能在没有VPU的情况下表达抑制病毒释放的限制因子。最近，骨髓基质抗原2(BST-2/HM124/CD317/tetherin)被确定为该因子。这篇综述将集中在过去四年中关于VPU在CD4下调和限制病毒从细胞释放中的作用的新发现。我们将把这些发现与病毒的发病机制联系起来，并提出关于BST-2作为限制因素的问题。
Human immunodeficiency virus type 1 (HIV-1) and several simian immunodeficiency viruses (SIV) encode for a transmembrane protein known as Vpu. While the smallest of the HIV-1 proteins, it has two important functions within virus-infected cells. The first of these functions is the down-regulation of the CD4 receptor to prevent its interaction with the HIV-1 envelope glycoprotein. Vpu interacts with the CD4 receptor in the rough endoplasmic reticulum (RER), resulting in its re-translocation across the RER and subsequent degradation via the proteasomal pathway. The second major function of the Vpu protein is to facilitate release of virus from infected cells. Previous studies have shown that virus release is cell type specific, suggesting that certain cells may express a restriction factor that inhibits virus release in the absence of Vpu. Recently, bone marrow stromal antigen 2 (BST-2/HM124/CD317/tetherin) has been identified as this factor. This review will focus on new findings within the last four years on the role of Vpu in CD4 down-regulation and the restriction of virus release from cells. We will relate these findings to virus pathogenesis and propose questions regarding BST-2 as a restriction factor.
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