The role of the structural domains of human BST-2 in inhibiting the release of xenotropic murine leukemia virus-related virus

BST-2 (bone marrow stromal cell antigen 2) is an interferon-inducible protein that inhibits the release of a variety of enveloped viruses by tethering viral particles to the cell surface. Xenotropic murine leukemia virus-related virus (XMRV) is a gamma-retrovirus that was derived from the recombination of two endogenous murine leukemia viruses during the production of a prostate cell line in mice. In this study, we observed that XMRV was highly sensitive to the inhibition by human BST-2. We were able to determine the structural domains of BST-2 that are essential to restrict XMRV, including the transmembrane domain, the coiled-coil ectodomain, the C-terminal glycosylphosphatidylinositol (GPI) anchor, the two putative N-linked glycosylation sites, and the three extracellular cysteine residues. Protease treatment effectively released XMRV particles into the supernatant, supporting the notion that BST-2 tethered nascent particles to the cell surface. These data suggest that BST-2 poses a strong restriction toward XMRV production.

► We show that BST-2 tethers nascent XMRV virions to cellular membranes.
► We determine the structural domains that are essential for BST-2 to restrict XMRV.
► Protease treatment releases the tethered XMRV particles from the cell surface.
► Illustrating the role of BST-2 structural domain in BST-2 cellular localization.