Antiviral inhibition of enveloped virus release by tetherin/BST-2: action and counteraction

Abstract

Tetherin (BST2/CD317) has been recently recognized as a potent interferon-induced antiviral molecule that inhibits the release of diverse mammalian enveloped virus particles from infected cells. By targeting an immutable structure common to all these viruses, the virion membrane, evasion of this antiviral mechanism has necessitated the development of specific countermeasures that directly inhibit tetherin activity. Here we review our current understanding of the molecular basis of tetherin's mode of action, the viral countermeasures that antagonize it, and how virus/tetherin interactions may affect viral transmission and pathogenicity.

Keywords: Tetherin/BST2; Vpu; interferon; restriction of enveloped virus release; viral countermeasure.

Figure 1

Features of tetherin. A schematic representation of the structural domains of tetherin is shown above an alignment of the human, chimpanzee (cpz) and sooty mangabey (smm) amino acid sequences. Black boxes around amino acids indicate regions important for the antiviral function of all three tetherin proteins. Red, blue and yellow boxes indicate amino acids important for the recognition and/or antagonism of tetherin by HIV-1 Vpu, HIV-2 Env and SIV Nef, respectively.

Figure 2

Schematic representation of tetherin and its lentiviral antagonists. The black arrows indicate regions of interaction between tetherin and each lentiviral antagonist, as detailed in the text. The tetherin species specificity of each lentiviral antagonist is indicated in the light grey boxes. Where known, the mechanism(s) by which the antagonists counteract tetherin are detailed in the dark grey boxes.