Sumoylation at the Host-Pathogen Interface

Wilson, Van G.

Not only is the SIM-SUMO interaction important for directing the anti-viral activity of PML NBs, there is increasing evidence that viruses use SIM-SUMO interactions to thwart the effects of PML. PML is itself sumoylated at three sites [68] , so PML accumulation at viral replication foci would contribute to the concentration of SUMO groups localized at these foci. Recent studies on herpes varicella-zoster virus (VSV) ORF61 protein showed that ORF61 has a functional SIM motif in the C-terminal domain, and that mutation of this SIM motif significantly impaired the ability of ORF61 to disperse NBs and strongly reduced co-localization of ORF61 with PML NBs [69] . Surprisingly, mutation of this SIM motif did not impair viral replication in permissive cells in vitro, but was required for pathogenesis and skin lesions in a SCID mouse model with human skin xenografts. While the mechanism by which ORF61 disperses PML is still unclear, these results strongly suggest that ORF61 targeting to NBs is mediated through the ORF61 SIM interacting with sumoylated proteins, possibly sumoylated PML.