An interferon-α-induced tethering mechanism inhibits HIV-1 and ebola virus particle release but is counteracted by the HIV-1 Vpu protein

Type 1 interferon (IFN) inhibits the release of HIV-1 virus particles via poorly defined mechanisms. Here, we show that IFN alpha induces retention of viral particles on the surface of fibroblasts, T cells, or primary lymphocytes infected with HIV-1 lacking the Vpu protein. Retained particles are tethered to cell surfaces, can be endocytosed, appear fully assembled, exhibit mature morphology, and can be detached by protease. Strikingly, expression of the HIV-1 Vpu protein attenuates the ability of human cells to adhere to, and thereby retain, nascent HIV-1 particles upon IFNa treatment. Vpu also counteracts the IFN alpha-induced retention of virus-like particles assembled from the Ebola virus matrix protein. Furthermore, levels of IFN alpha that suppress replication of Vpu-defective HIV-1 have little effect on wild-type HIV-1. Thus, we propose that HIV-1 expresses Vpu to counteract an IFN alpha-induced, general host defense that inhibits dissemination of enveloped virions from the surface of infected cells.