Bone marrow stromal cell antigen 2 (BST-2) restricts mouse mammary tumor virus (MMTV) replication in vivo

By using RNA interference, we show that loss of BST-2 enhances MMTV replication in cultured mammary tumor cells and in vivo. In cultured cells, BST-2 inhibits virus accumulation in the culture medium, and co-localizes at the cell surface with virus structural proteins. Furthermore, both scanning electron micrograph (SEM) and transmission electron micrograph (TEM) show that MMTV accumulates on the surface of IFNα-stimulated cells.Our data provide evidence that BST-2 restricts MMTV release from naturally infected cells and that BST-2 is an antiviral factor in vivo.Bone marrow stromal cell antigen 2 (BST-2) protein also known as tetherin/CD317 is a potent restriction factor against a wide range of enveloped viruses such as HIV, FIV, KSHV, MMTV, SIV, Lassa, Marbug, Ebola, and MLV [1-5]. BST-2 achieves its anti-viral effect by connecting both viral and host cell membranes, thus preventing virus egress [6-9]. While BST-2 inhibits virus release, most viruses including HIV-1, HIV-2, and Ebola virus have developed strategies to antagonize BST-2 by degradation, down-regulation of expression, or reduction of its steady-state level [1,2,7,10-14]. In addition to inhibiting virus egress and virus replication in cell culture, there is evidence that, following interferon-induction, BST-2 is up-regulated and incorporated into budding virions [2,6,8,9]. While the antiviral activity of BST-2 has been demonstrated in tissue culture cells, there has been no evidence that BST-2 exerts antiviral activity in vivo. In this context, we evaluated the ability of mouse BST-2 to restrict the replication of the exogenous murine retrovirus mouse mammary tumor virus (MMTV) in cell culture and in mice.In vivo, MMTV first infects antigen presenting cells (APCs) such as B cells and dendritic cells (DCs) at the site of infection [15-19]. MMTV infected APCs present virus-encoded superantigen (Sag) to T cells expressing Sag-specific T-cell receptor (TCR) Vβ chains. This immunological synapse causes stimu