Vpu targets BST-2 to deregulate the interferon response

Paula Cannon
University of Southern California
Basic Biomedical Sciences

A puzzling aspect of HIV-1 infection is that the body’s classic anti-viral response – the production of interferon (IFN) – does not seem to protect against this virus, since higher levels of IFN are associated with worse disease outcomes. Most IFN is produced from a specialized cell type called plasmacytoid dendritic cells (pDCs).  Normally, IFN is produced from pDCs for only a short period of time, and its production is limited by the action of the BST-2 protein, which binds to and activates the ILTR7 receptor on the surface of pDCs.  Interestingly, HIV-1 has a protein, Vpu, that blocks the expression of BST-2 on the surface of infected cells. We hypothesize that this action of Vpu has evolved to maintain high levels of pDC activation and keep IFN production switched on, and that this in some way drives HIV-1 pathogenesis. In order to test this hypothesis we will set up systems in cell culture and in vivo to explore the ability of the Vpu protein to influence IFN production from pDCs. Understanding whether the virus has evolved to stimulate IFN production, and the mechanism that drives this, may suggest new therapeutic approaches to limit the pathogenic consequences of HIV infection.