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: To investigate the potential significance of the accumulation of HMW SUMO-conjugated proteins during ICP0- mutant HSV-1 infection, the SUMO E3 ligase(s) that could mediate these SUMOylation events was analyzed, starting with the PIAS protein family. Consistent with other reports, PIAS proteins in HFt cells were predominantly nuclear, with microspeckled distributions characteristic of localization at matrix-associated regions (MARs) (Fig. 2A to D, mock) (65–67). While a subpopulation of PIAS1 localized to PML-NBs, substantial localization of PIAS2, PIAS3, or PIAS4 at these structures was not detected in this cell type (Fig. 2A to D, mock, and data not shown) (38, 66). PIAS4 robustly relocalized to viral replication compartments, whereas PIAS1, PIAS2, and PIAS3 did not (Fig. 2A to D). The relocalization of PIAS4 was independent of ICP0, as it occurred during wild-type or ICP0- mutant HSV-1 infection (Fig. 2D). PIAS4 is thus identified as a SUMO E3 ligase that accumulates in herpesvirus replication compartments. SUMO2/3 also accumulated in HSV-1 replication compartments, although only in the absence of ICP0 (Fig. 2E). Therefore, during ICP0- mutant HSV-1 infection, the majority of nuclear PIAS4 and SUMO2/3 localize in replication compartments.
Affiliation: MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow, Scotland, United Kingdom.