Sumoylation at the Host-Pathogen Interface

Wilson, Van G.

ot inhibit sumoylation of PML in vitro [115] . A model proposed by the authors is that direct interaction of IE1 with PML induces disaggregation of NBs that subsequently exposes released PML to cellular SUMO proteases. In this scenario the desumoylation of PML would be indirectly mediated by this viral early protein. The situation with IE2 is even less clear. The initial observation was that IE2 expressed alone co-localized with NBs though this did not lead to NB disruption [107] . While IE2 is sumoylated [116] , interacts with both Ubc9 [117] and PIAS1 [118] , and has a SIM motif [119, 120] , a study by Sourvinos et al. found that targeting of IE2 to NBs was via association with viral genomes [121] . Consequently, while IE2 is important for viral replication there is little evidence that it plays a role in overcoming the antiviral effect of PML, and this role may be primarily the purview of IE1. In summary, members of the herpesvirus family express early proteins that target PML NBs, and most of these proteins utilize SIM motifs to facilitate their interaction with sumoylated PML. Many of these PML binding herpesvirus proteins subsequently affect the sumoylation status of PML to promote dissemble of the NBs, though they do so through diverse mechanism.