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: The accumulation of endogenous PIAS4 in HSV-1 replication compartments increased in prominence as infection progressed, which could result from accumulation of PIAS4, an increase in PIAS4 protein expression, or both. The expression levels of PIAS4 were therefore evaluated in HFt cells infected with 10 PFU per cell of wild-type or ICP0- mutant HSV-1. As infection progressed, endogenous PIAS4 protein levels increased (Fig. 10A and B). This increase was most prominent during wild-type infection, demonstrating that PIAS4 is not a target for ICP0-mediated degradation (Fig. 10A and B). Inhibition of the proteasome did not further enhance PIAS4 protein levels (Fig. 10A and B, +MG132), indicating that this increase was largely not achieved through changes to PIAS4 turnover rates. Although PIAS4 protein levels increased, PIAS4 mRNA levels remained largely unchanged (Fig. 10C), supporting the notion that PIAS4 does not correspond to an interferon-stimulated gene (ISG) (72). Together, these data suggest that the increase in PIAS4 protein levels is likely the result of changes to its translational or posttranslational regulation rather than changes to its transcription or protein turnover rates.
Affiliation: MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow, Scotland, United Kingdom.