TBC1 Domain Family, Member 21 (TBC1D21)

TBC1D21 Contains 1 Rab-GAP TBC domain. Rab-GAP TBC domain protein binds hepatitis C virus NS5A and mediates viral replication. This partner contains a TBC Rab-GAP homology domain found in all known Rab-activating proteins. As the first described interaction between such a Rab-GAP and a viral protein, this finding suggests a new mechanism whereby viruses may subvert host cell machinery for mediating the endocytosis, trafficking, and sorting of their own proteins. Moreover, depleting the expression of this partner severely impairs HCV RNA replication with no obvious effect on cell viability. These results suggest that pharmacologic disruption of this NS5A-interacting partner can be contemplated as a potential new antiviral strategy against a pathogen affecting nearly 3% of the world's population.