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
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Mentions: During ICP0- mutant HSV-1 infection, eYFP.PIAS4 also localized to nuclear domains that contained infecting viral genomes (Fig. 8B) (6, 8, 69). This localization was SIM dependent (Fig. 8C to I), consistent with the SIM-dependent recruitment of evaluated constituent PML-NB antiviral proteins (17). However, high levels of eYFP.PIAS4 expression disrupted the SIM-dependent recruitment of constituent PML-NB antiviral proteins without disrupting its own recruitment (Fig. 9). The global depletion of free SUMO pools as a consequence of high levels of eYFP.PIAS4 expression likely precluded the de novo SUMOylation events that mediate recruitment of constitutive PML-NB antiviral proteins (Fig. 4A and B and 9) (17, 18). In contrast, de novo SUMOylation, higher levels of free SUMO, or constituent PML-NB antiviral proteins were not required for the recruitment of eYFP-PIAS4 to domains that contained infecting HSV-1 genomes (Fig. 9A). Moreover, under conditions of depleted free SUMO pools, eYFP.PIAS4 was not sufficient to recruit constituent PML-NB antiviral proteins to nuclear domains that contained infecting HSV-1 genomes (Fig. 9).
Affiliation: MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow, Scotland, United Kingdom.