BST-2/tetherin: Structural biology, viral antagonism, and immunobiology of a potent host antiviral factor

BST-2 (also known as tetherin, CD317, or HM1.24) was first described as a potent interferon-inducible host antiviral factor nearly five years ago. Since that time, numerous reports have been published regarding the antiviral activity and immunological properties of this protein. BST-2 blocks viral replication by inhibiting enveloped virus budding from the surface of infected cells. To counteract this, most viruses have developed strategies to antagonize BST-2, each employing a unique mechanism. In this review, we summarize the antiviral function, structural biology and immunobiology of BST-2. Taken together, our current understanding of BST-2 suggests potential avenues as well as challenges to exploiting its action in the development of broad spectrum antiviral treatments.

► BST-2 is a host antiviral protein that inhibits release of progeny enveloped viruses from infected cells.
► Inhibition may occur by direct tethering or arresting scission.
► Unique structural features of the ectodomain optimize it for function.
► Viruses encode antagonists that inhibit BST-2 via diverse mechanisms.
► Analysis of mice suggests other biologic functions.