Sumoylation at the Host-Pathogen Interface

Wilson, Van G.

In addition to classical innate immunity mediated through interferons and cytokines, the concept of intrinsic immunity has developed in recent years [53] . Unlike the induction cascade required to activate innate immunity, intrinsic immunity operates through pre-existing proteins that act to repress viral infection. Several members of the TRIM family of proteins have been shown to participate in intrinsic immunity, and while some can be up regulated by interferon, their anti-viral activity does not directly require interferon [54] . There is now mounting evidence that sumoylation is important in directing TRIM proteins to their targets. For example, the cytoplasmic TRIM5α protein can block certain retroviral infections [55, 56] . A recent publication demonstrated that TRIM5α has three potential SUMO-interacting motifs (SIMs) and that the anti-viral activity of TRIM5α requires SIM1 and SIM2, but not SIM3 [57] . Mutations in the murine leukemia virus (MLV) capsid antigen (CA) that blocked CA sumoylation abrogated the ability of TRIM5α to restrict MLV replication. From these results the authors propose that restriction by TRIM5α, at least in part, involves direct binding of TRIM5α to sumoylated CA through the SIM1 and SIM2 regions in TRIM5α. This SUMO-SIM facilitated interaction presumably then leads to some change in capsid structure that disrupts the normal infection process and restricts viral infection.