Seminar: Sonja Best

Beyond retroviruses: New effector functions for the antiviral restriction factor TRIM5a

TRIpartite Motif (TRIM) proteins belong to a large protein family, many of which are inducible by type I interferon and serve to suppress virus infection through direct interactions with viral proteins. Primate TRIM5α is a consequential inhibitor that suppresses lentivirus replication (e.g HIV-1) in a highly host species- and virus species-specific fashion to limit cross-species transmission of these viruses. Importantly, the antiviral effects of TRIM5α have been thought to function exclusively in the context of lentivirus infection. Our research interests center on the orthoflaviviruses that include significant pathogens that have emerged into human populations from primates (e.g. dengue virus, Zika virus, yellow fever virus) prompting us to determine whether TRIM5α could also function to inhibit orthoflavivirus replication. Surprisingly, this work has revealed a new function for TRIM5α as a potent restriction factor for replication of specific orthoflaviviruses. The mechanisms of restriction, orthoflavivirus escape, and the implications of TRIM5a as an early barrier to orthoflavivirus replication and host immunity will be discussed.