Summer Research Description: The HIV-1 capsid, which forms the shell surrounding the viral RNA genome, plays crucial roles throughout the processes of early infection. In nonhuman primate cells, the host factors TRIM5α and TRIMCyp restrict retroviral infection by binding to the viral capsid and promoting its premature disassembly. In rhesus macaques and owl monkeys, TRIM5α and TRIMCyp, respectively, restrict HIV-1 infection at multiple early stages including reverse transcription and nuclear entry. Multiple host cofactors involved in the TRIM5α-mediated block to reverse transcription have previously been identified. We hypothesize that TRIM5α and TRIMCyp, through interactions with the viral capsid, modulate interactions with additional host cofactors to facilitate restriction to HIV-1 infection. To identify capsid-interacting cofactors, we will perform binding assays with recombinant capsid protein and human cell lysates expressing TRIM5α or TRIMCyp. Capsid-binding host factors will be identified by mass spectrometry. Understanding the mechanism of TRIM5α- and TRIMCyp-mediated restriction will aid in clarification of the process of capsid disassembly and may provide opportunities to target this pathway for the development of novel therapeutics.