Mammals have evolved a variety of innate cellular defences that block the replication of retroviruses. Primate lentiviruses in turn have developed mechanisms to evade these host restrictions, helping them to establish chronic infections that, in the case of Human Immunodeficiency Viruses (HIV), eventually lead to AIDS. My interest is in how the small accessory protein Vpu, encoded by HIV-1, overcomes such a cellular defence. We identified a human IFN-induced plasma membrane protein, Tetherin/CD317 that restricts retroviral particle release but can be overcome by Vpu expression. Tetherin/CD317 has an unusual topology and traffics between multiple cellular compartments. Understanding the cellular and molecular basis for Vpu antagonism of Tetherin-mediated restriction of HIV-1 release should indicate novel targets for antiretroviral drug development.

Human immunodeficiency virus; tetherin; antiviral restriction; Vpu