Grant: Foundation Grant

Human immunodeficiency virus (HIV) remains a global health challenge. Despite the significant advances made over the past decades with respect to our understanding of how HIV causes AIDS, the hope for a definitive cure has been frustrated by the seemingly endless propensity of HIV to subvert host defenses and to persist in long-lived viral reservoirs (VR) that cannot be eliminated by current antiretroviral therapies (ART). While ART have dramatically improved the prognosis for infected individuals, they are not curative because of the persistence of VRs. HIV eludes host immune defenses and establishes VRs in part because it encodes a set of small accessory proteins, whose function is to overcome various types of antiviral immune response. My Team discovered and characterized two of the six accessory proteins encoded by HIV and we are world leaders in understanding the role of these virulence factors in HIV transmission, pathogenesis and persistence. Given their crucial roles in overcoming host defense mechanisms, these accessory proteins are attractive targets for the design of HIV cure strategies aimed at eradicating persistent HIV infection. Our research program will focus primarily on two of the accessory proteins encoded by HIV-1, namely Viral protein U (Vpu) and Viral Protein R (Vpr), to unravel the full spectrum of their activities and better define their functions in HIV persistence, to elucidate how they operate at the molecular and cellular levels and to identify new areas of their biology that are applicable to therapeutic intervention. This work will uncover viral and host targets for HIV persistence reversal and provide new insights that will inform and guide HIV cure strategies. While conducting these studies, our dynamic and forward-looking training and mentoring program will provide trainees with a conceptually and technically deep experience and skills that are sought by employers in academia, government and the private sector