A novel role for Protein Inhibitor of Activated STAT 4 ( PIAS 4 ) in the restriction of herpes 1 simplex virus 1 ( HSV-1 ) by the cellular intrinsic antiviral immune response

24 Small Ubiquitin like MOdifier (SUMO) is used by the intrinsic antiviral immune response to 25 restrict viral pathogens, such as Herpes Simplex Virus 1 (HSV-1). Despite characterization of 26 the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that 27 mediate these SUMOylation events remain to be defined. We show that unconjugated SUMO 28 levels are largely maintained throughout infection regardless of the presence of ICP0, the HSV-1 29 SUMO-targeted ubiquitin ligase. Moreover, in the absence of ICP0, high molecular weight 30 SUMO-conjugated proteins do not accumulate if HSV-1 DNA does not replicate. These data 31 highlight the continued importance for SUMO signaling throughout infection. We show that the 32