The relative ability of cell autonomous HIV-1 restriction factors to interfere with the viral life cycle contributes to a host’s level of susceptibility to infection. Pharmacological enhancement of restriction factor efficacy would be a novel approach to treating HIV infection. However, the mechanistic basis for HIV blockage by restriction factors is not completely understood hampering efforts to employ restriction factor-based host directed therapies.
Members of the TRIM family of proteins have been identified as being capable of limiting the ability of HIV to infect and replicate within cells, but the mechanism(s) underlying their action have not been fully uncovered. In this proposal, we test the hypothesis that autophagy, a pathway that can be manipulated with existing drugs, underlies the action of TRIM proteins in antiviral defense. These studies will further our understanding of the cellular functions of TRIM proteins at a molecular level and may provide the groundwork for therapeutic approaches to the diverse diseases, including HIV/AIDS, in which TRIMs play a role.