Grant: Operating Grant

AIDS is a slow degenerative disease of the immune and nervous systems resulting from HIV-1 infection. Despite considerable progress made in our understanding of HIV-1 infection, we still do not completely understand how the virus causes AIDS and how it maintains itself in infected individuals in presence of a vigorous immune response and highly suppressive antiretroviral regimens. Ultimately, our ability to control the AIDS pandemics, already destined to claim more than 33 million of lives world-wide, will depend on our ability: i) to interrupt effectively viral replication, transmission and persistence by developing novel antiviral strategies; ii) to render host antiviral immune responses more efficient at preventing viral infection by developing safe vaccine strategies. The HIV-1 vpu gene encodes a small integral membrane protein that is not found in HIV-2 and most simian immunodeficiency viruses. Vpu promotes the production of HIV-1 by antagonizing a newly identified interferon-regulated host restriction factor,called Tetherin/BST2, that retains newly formed virions at the surface of infected cells. The exact mechanisms underlying Tetherin antagonism by Vpu are yet to be elucidated. Furthermore, the role of Tetherin and Vpu in relevant cell targets of HIV-1 remains to be fully defined. Finally, given that the interaction of Vpu with Tetherin represents a potential therapeutic target, it is unclear whether HIV-1 can resist Tetherin restriction through Vpu-independent mechanism(s). The goal of this research project will be to continue our investigation on the function and mode of action of Vpu to develop a better understanding of key HIV-1-host interactions regulating virus release and transmission. Ultimately, elucidation of the interaction between HIV-1 Vpu and host innate defenses will lead to a heightened comprehension of viral replication and pathogenesis as well as suggesting additional targets for antiviral strategies.