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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.

Conn KL, Wasson P, McFarlane S, Tong L, Brown JR, Grant KG, Domingues P, Boutell C - J. Virol. (2016)

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.

View Article: PubMed Central - PubMed

Affiliation: MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow, Scotland, United Kingdom.

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Related in: MedlinePlus

Overexpression of eYFP.PIAS4 disrupts the recruitment of PML-NB antiviral proteins to domains that contain infecting HSV-1 genomes in an SP-RING-dependent manner. (A and B) Confocal images show the recruitment of constituent PML-NB antiviral proteins to nuclear domains associated with HSV-1 genome entry in transgenic cells that express eYFP.PIAS4 wild-type (wt; A) or catalytically inactive mutant (C342A; B) proteins. Transgenic HFt cells were induced with DOX for 16 h before they were infected with 1 PFU of ICP0- mutant (ΔICP0) HSV-1 per cell for 24 h. The nuclear domains that contain infecting HSV-1 genomes were identified by nuclear edge localization of ICP4. PML, Sp100, Daxx, SUMO1, or SUMO2/3 (cyan) and ICP4 (red) were visualized by indirect immunofluorescence.
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Figure 9: Overexpression of eYFP.PIAS4 disrupts the recruitment of PML-NB antiviral proteins to domains that contain infecting HSV-1 genomes in an SP-RING-dependent manner. (A and B) Confocal images show the recruitment of constituent PML-NB antiviral proteins to nuclear domains associated with HSV-1 genome entry in transgenic cells that express eYFP.PIAS4 wild-type (wt; A) or catalytically inactive mutant (C342A; B) proteins. Transgenic HFt cells were induced with DOX for 16 h before they were infected with 1 PFU of ICP0- mutant (ΔICP0) HSV-1 per cell for 24 h. The nuclear domains that contain infecting HSV-1 genomes were identified by nuclear edge localization of ICP4. PML, Sp100, Daxx, SUMO1, or SUMO2/3 (cyan) and ICP4 (red) were visualized by indirect immunofluorescence.

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.


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.

Conn KL, Wasson P, McFarlane S, Tong L, Brown JR, Grant KG, Domingues P, Boutell C - J. Virol. (2016)

Overexpression of eYFP.PIAS4 disrupts the recruitment of PML-NB antiviral proteins to domains that contain infecting HSV-1 genomes in an SP-RING-dependent manner. (A and B) Confocal images show the recruitment of constituent PML-NB antiviral proteins to nuclear domains associated with HSV-1 genome entry in transgenic cells that express eYFP.PIAS4 wild-type (wt; A) or catalytically inactive mutant (C342A; B) proteins. Transgenic HFt cells were induced with DOX for 16 h before they were infected with 1 PFU of ICP0- mutant (ΔICP0) HSV-1 per cell for 24 h. The nuclear domains that contain infecting HSV-1 genomes were identified by nuclear edge localization of ICP4. PML, Sp100, Daxx, SUMO1, or SUMO2/3 (cyan) and ICP4 (red) were visualized by indirect immunofluorescence.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4836348&req=5

Figure 9: Overexpression of eYFP.PIAS4 disrupts the recruitment of PML-NB antiviral proteins to domains that contain infecting HSV-1 genomes in an SP-RING-dependent manner. (A and B) Confocal images show the recruitment of constituent PML-NB antiviral proteins to nuclear domains associated with HSV-1 genome entry in transgenic cells that express eYFP.PIAS4 wild-type (wt; A) or catalytically inactive mutant (C342A; B) proteins. Transgenic HFt cells were induced with DOX for 16 h before they were infected with 1 PFU of ICP0- mutant (ΔICP0) HSV-1 per cell for 24 h. The nuclear domains that contain infecting HSV-1 genomes were identified by nuclear edge localization of ICP4. PML, Sp100, Daxx, SUMO1, or SUMO2/3 (cyan) and ICP4 (red) were visualized by indirect immunofluorescence.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow, Scotland, United Kingdom.

Show MeSH
Related in: MedlinePlus