Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response.
Bottom Line: Despite characterization of the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that mediate these SUMOylation events remain to be defined.Moreover, in the absence of ICP0, high-molecular-weight SUMO-conjugated proteins do not accumulate if HSV-1 DNA does not replicate.The protein inhibitor of activated STAT (PIAS) family of SUMO ligases is predominantly associated with the suppression of innate immune signaling.
Affiliation: MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow, Scotland, United Kingdom.Show MeSH
Related in: MedlinePlus
Mentions: The subnuclear localization of mutant eYFP.PIAS4 proteins was initially evaluated during ICP0- mutant HSV-1 infection to avoid potential ICP0-mediated disruption of relevant interactions. EYFP alone did not accumulate in replication compartments, while eYFP.PIAS4 did (Fig. 6A and B), demonstrating that fusion to eYFP did not adversely affect PIAS4 localization. However, endogenous PIAS4 tended to localize throughout individual replication compartments, whereas eYFP.PIAS4 tended to occupy subdomains within them (Fig. 6B and J). Notably, endogenous or exogenous PIAS4 could colocalize with PML, a known intrinsic antiviral factor (Fig. 6B, K, and L). The regions where eYFP.PIAS4 and PML colocalized were largely restrained to subdomains within individual replication compartments and often resembled string-like structures (Fig. 6B, inset) (69).
Affiliation: MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow, Scotland, United Kingdom.