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: In the absence of ICP0, the accumulation of HMW SUMO-conjugated proteins was most prominent at later times after infection (Fig. 1A and B, 9 hpi). To evaluate whether HSV-1 DNA replication or late (L) protein expression contributed to this accumulation, HFt cells were infected with 10 PFU per cell of ICP0- mutant HSV-1 in the presence or absence of phosphonoacetic acid (PAA) to inhibit the HSV-1 DNA polymerase, or acycloguanosine (ACG) to inhibit nascent DNA synthesis (61–64). In the absence of viral DNA replication, the levels of HMW SUMO1- or SUMO2/3-conjugated proteins, as well as the levels of free SUMO1 or SUMO2/3, remained similar to those in mock-infected cells (Fig. 1C). The SUMOylation events that result in the accumulation of HMW SUMO-conjugated proteins therefore occur when HSV-1 DNA replicates or L proteins are expressed. Viral transcription in general, or the expression of IE or E proteins, was not sufficient to stimulate this broad accumulation of HMW SUMO-conjugated proteins during ICP0- mutant HSV-1 infection.
Affiliation: MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow, Scotland, United Kingdom.