Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu

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.