Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu
Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu
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DOI：
10.1038/nature06553
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发表时间：
2008-01-24
期刊：
影响因子：
64.8
通讯作者：
Bieniasz, Paul D.
中科院分区：
文献类型：
--
作者：
Neil, Stuart J. D.;Zang, Trinity;Bieniasz, Paul D.
人类细胞具有抑制逆转录病毒颗粒和其他包膜病毒颗粒释放的抗病毒活性，并被HIV- 1辅助蛋白Vpu拮抗。这种抗病毒活性可以由干扰素-α组成型表达或诱导，并且它由基于蛋白质的系链组成，我们称之为“系链蛋白”，其导致完全形成的病毒体保留在感染的细胞表面上。使用演绎约束和基因表达分析，我们确定CD 317（也称为BST 2或HM 1.24），以前未知的功能的膜蛋白，作为一个拴蛋白。具体而言，CD 317的表达相关，并诱导，在HIV- 1和小鼠白血病病毒颗粒释放的Vpu的要求。此外，在HIV- 1病毒体释放需要Vpu表达的细胞中，CD 317的消耗消除了这一要求。CD 317引起病毒粒子滞留在细胞表面，并在胞吞作用后滞留在CD 317阳性隔室中。Vpu与CD 317共定位并抑制这些作用。Vpu功能的抑制和随之而来的tetherin的抗病毒活性的动员是HIV/AIDS的潜在治疗策略。
Human cells possess an antiviral activity that inhibits the release of retrovirus particles, and other enveloped virus particles, and is antagonized by the HIV- 1 accessory protein, Vpu. This antiviral activity can be constitutively expressed or induced by interferon-alpha, and it consists of protein- based tethers, which we term 'tetherins', that cause retention of fully formed virions on infected cell surfaces. Using deductive constraints and gene expression analyses, we identify CD317 ( also called BST2 or HM1.24), a membrane protein of previously unknown function, as a tetherin. Specifically, CD317 expression correlated with, and induced, a requirement for Vpu during HIV- 1 and murine leukaemia virus particle release. Furthermore, in cells where HIV- 1 virion release requires Vpu expression, depletion of CD317 abolished this requirement. CD317 caused retention of virions on cell surfaces and, after endocytosis, in CD317- positive compartments. Vpu co- localized with CD317 and inhibited these effects. Inhibition of Vpu function and consequent mobilization of tetherin's antiviral activity is a potential therapeutic strategy in HIV/AIDS.