My research, which is performed in close collaboration with Dr. Vojo Deretic, focuses on the autophagic targeting of HIV-1 by members of the TRIM family of proteins (TRIMs). This protein family consists of more than 70 members in humans, with individual members affecting innate immunity, inflammation, and antiviral defense, although in most cases their mode of action has remained elusive. As detailed in a study published in Developmental Cell (August 2014), I found that TRIMs have dual roles in selective autophagy: as regulators and as cargo receptors. TRIM5α, a well-known anti-HIV restriction factor, promoted autophagy by acting as a platform for the assembly of autophagy initiation factors in their activated states. Furthermore, via interactions with both HIV-1 capsid and with proteins associated with autophagosome membranes, TRIM5α delivered HIV-1 for autophagic degradation. As part of my studies with TRIM5α, I found that many if not all TRIMs also regulate autophagy and have the capability to be selective autophagy receptors. As several TRIMs in addition to TRIM5α are known to protect cells against retroviral infection, my future studies will focus on testing the hypothesis that autophagy is their underlying mode of action in retroviral restriction.
