Transmembrane Interactions of HIV-1 Vpu and Tetherin

Abstract

Tetherin is a type II membrane protein that bears a N-terminal transmembrane domain, an extracellular coiled-coil structure and a C-terminal GPI anchor. This unique topology allows tetherin to block the release of a wide range of enveloped viruses from the cell surface. In order to overcome this host restriction, viruses have evolved various counter measures. In the case of human immunodeficiency virus type 1 (HIV-1), the viral protein U (Vpu) is able to down-modulate cell surface tetherin, thus removing tetherin molecules from the site of virus budding. This activity of Vpu depends on its direct interaction with tetherin. In this review, we summarize the known molecular details of the interaction between Vpu and tetherin, and also discuss how tetherin is targeted by other viral antagonists. Following our summary, it is evident that each of the intracellular, transmembrane and extracellular domains of tetherin can become the target of viral antagonists for counteraction.