Neil Stuart J D, Zang Trinity, Bieniasz Paul D
Aaron Diamond AIDS Research Center and Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, New York 10016, USA.
Nature. 2008 Jan 24;451(7177):425-30. doi: 10.1038/nature06553. Epub 2008 Jan 16.
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.
人类细胞具有一种抗病毒活性，可抑制逆转录病毒颗粒以及其他包膜病毒颗粒的释放，而HIV-1辅助蛋白Vpu可对抗这种活性。这种抗病毒活性可以组成性表达，也可由α干扰素诱导产生，它由基于蛋白质的连接物组成，我们将其称为“连接蛋白”，这些连接蛋白可使完全形成的病毒体滞留在受感染细胞表面。通过演绎性限制和基因表达分析，我们确定CD317（也称为BST2或HM1.24），一种功能未知的膜蛋白，为连接蛋白。具体而言，CD317的表达与HIV-1和小鼠白血病病毒颗粒释放过程中对Vpu的需求相关并可诱导这种需求。此外，在HIV-1病毒体释放需要Vpu表达的细胞中，去除CD317可消除这种需求。CD317可使病毒体滞留在细胞表面，并且在胞吞作用后，滞留在CD317阳性区室中。Vpu与CD317共定位并抑制这些作用。抑制Vpu功能并随之调动连接蛋白的抗病毒活性是治疗HIV/AIDS的一种潜在策略。
