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Herpes simplex virus 1 UL41 protein abrogates the antiviral activity of hZAP by degrading its mRNA.

Su C, Zhang J, Zheng C - Virol. J. (2015)

Bottom Line: However, previous study demonstrated that ectopic expression of rat ZAP did not suppress the replication of herpes simplex virus type 1 (HSV-1), an archetypal member of the alphaherpesvirus subfamily, and the molecular mechanism underneath is still illusive.Moreover, ectopic expression of hZAP inhibited the replication of R2621 but not WT HSV-1.HSV-1 UL41 was shown for the first time to evade the antiviral function of hZAP via its RNase activity.

View Article: PubMed Central - PubMed

Affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China. such1986@aliyun.com.

ABSTRACT

Background: The zinc finger antiviral protein (ZAP) is a host restriction factor that inhibits the replication of various viruses by degradation of certain viral mRNA. However, previous study demonstrated that ectopic expression of rat ZAP did not suppress the replication of herpes simplex virus type 1 (HSV-1), an archetypal member of the alphaherpesvirus subfamily, and the molecular mechanism underneath is still illusive.

Results: Human ZAP (hZAP) does not suppress the replication of herpes simplex virus 1, and HSV-1 UL41 protein was identified as an antagonist of hZAP by degrading its mRNA. Infection of wild-type (WT), but not UL41- mutant (R2621) virus, diminished the accumulation of hZAP to abrogate its antiviral activity. Moreover, ectopic expression of hZAP inhibited the replication of R2621 but not WT HSV-1.

Conclusion: HSV-1 UL41 was shown for the first time to evade the antiviral function of hZAP via its RNase activity.

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Related in: MedlinePlus

Expression of hZAP inhibits UL41- mutant HSV-1 R2621 infection. a and b 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1 or R2621 at an MOI of 1, respectively. At 2 h post-infection, cells were mock treated or treated with tetracycline (1000 ng/mL). At 36 h post-infection, cells were lysed and subjected to WB analysis with the indicated Ab. c and d 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1. After 2 h post-infection, cells were treated with or without Tet (1000 ng/mL) to induce hZAPL or hZAPS expression. Viral growth curves were generated by traditional plaque assays at the indicated time points. e and f 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with R2621 virus. After 2 h post-infection, cells were treated with or without Tet (1000 ng/mL) to induce hZAPL or hZAPS expression. Viral growth curves were generated by traditional plaque assays at the indicated time points. One representative of three independent experiments was shown. (*P < 0.05)
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Fig4: Expression of hZAP inhibits UL41- mutant HSV-1 R2621 infection. a and b 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1 or R2621 at an MOI of 1, respectively. At 2 h post-infection, cells were mock treated or treated with tetracycline (1000 ng/mL). At 36 h post-infection, cells were lysed and subjected to WB analysis with the indicated Ab. c and d 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1. After 2 h post-infection, cells were treated with or without Tet (1000 ng/mL) to induce hZAPL or hZAPS expression. Viral growth curves were generated by traditional plaque assays at the indicated time points. e and f 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with R2621 virus. After 2 h post-infection, cells were treated with or without Tet (1000 ng/mL) to induce hZAPL or hZAPS expression. Viral growth curves were generated by traditional plaque assays at the indicated time points. One representative of three independent experiments was shown. (*P < 0.05)

Mentions: Our previous results suggested that HSV-1 UL41 protein reduced the antiviral activity of hZAP by degradating its mRNA. However, the UL41- virus R2621 exerts no such function, which leads us to wonder whether hZAP could inhibit R2621 infection. Thus, 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1 or R2621 at an MOI of 1. At 2 h post-infection, the cells were treated or mock treated with tetracycline (1000 ng/mL). Western blot (WB) was performed to analyze the replication of these viruses 36 h post infection. As a result, the expression levels of ICP0 and UL46 in WT HSV-1 infected hZAPS and hZAPL-expression cells were similar to the WT HSV-1 infected mock treated cells. While the expression levels of ICP0 and UL46 in R2621 infected cells were inhibited by hZAPS or hZAPL expression compared to the R2621 infected mock treated cells (Fig. 4a, b). WT HSV-1 or R2621 viral growth curves were also examined through viral plague assays. As a result, ectopic expression of hZAPL or hZAPS inhibited UL41- HSV-1 replication, but not WT HSV-1 replication (Fig. 4c-f). Taken together, these results indicate UL41 promotes HSV-1 infection by antagonizing the antiviral activity of hZAP.Fig. 4


Herpes simplex virus 1 UL41 protein abrogates the antiviral activity of hZAP by degrading its mRNA.

Su C, Zhang J, Zheng C - Virol. J. (2015)

Expression of hZAP inhibits UL41- mutant HSV-1 R2621 infection. a and b 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1 or R2621 at an MOI of 1, respectively. At 2 h post-infection, cells were mock treated or treated with tetracycline (1000 ng/mL). At 36 h post-infection, cells were lysed and subjected to WB analysis with the indicated Ab. c and d 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1. After 2 h post-infection, cells were treated with or without Tet (1000 ng/mL) to induce hZAPL or hZAPS expression. Viral growth curves were generated by traditional plaque assays at the indicated time points. e and f 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with R2621 virus. After 2 h post-infection, cells were treated with or without Tet (1000 ng/mL) to induce hZAPL or hZAPS expression. Viral growth curves were generated by traditional plaque assays at the indicated time points. One representative of three independent experiments was shown. (*P < 0.05)
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4666169&req=5

Fig4: Expression of hZAP inhibits UL41- mutant HSV-1 R2621 infection. a and b 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1 or R2621 at an MOI of 1, respectively. At 2 h post-infection, cells were mock treated or treated with tetracycline (1000 ng/mL). At 36 h post-infection, cells were lysed and subjected to WB analysis with the indicated Ab. c and d 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1. After 2 h post-infection, cells were treated with or without Tet (1000 ng/mL) to induce hZAPL or hZAPS expression. Viral growth curves were generated by traditional plaque assays at the indicated time points. e and f 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with R2621 virus. After 2 h post-infection, cells were treated with or without Tet (1000 ng/mL) to induce hZAPL or hZAPS expression. Viral growth curves were generated by traditional plaque assays at the indicated time points. One representative of three independent experiments was shown. (*P < 0.05)
Mentions: Our previous results suggested that HSV-1 UL41 protein reduced the antiviral activity of hZAP by degradating its mRNA. However, the UL41- virus R2621 exerts no such function, which leads us to wonder whether hZAP could inhibit R2621 infection. Thus, 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1 or R2621 at an MOI of 1. At 2 h post-infection, the cells were treated or mock treated with tetracycline (1000 ng/mL). Western blot (WB) was performed to analyze the replication of these viruses 36 h post infection. As a result, the expression levels of ICP0 and UL46 in WT HSV-1 infected hZAPS and hZAPL-expression cells were similar to the WT HSV-1 infected mock treated cells. While the expression levels of ICP0 and UL46 in R2621 infected cells were inhibited by hZAPS or hZAPL expression compared to the R2621 infected mock treated cells (Fig. 4a, b). WT HSV-1 or R2621 viral growth curves were also examined through viral plague assays. As a result, ectopic expression of hZAPL or hZAPS inhibited UL41- HSV-1 replication, but not WT HSV-1 replication (Fig. 4c-f). Taken together, these results indicate UL41 promotes HSV-1 infection by antagonizing the antiviral activity of hZAP.Fig. 4

Bottom Line: However, previous study demonstrated that ectopic expression of rat ZAP did not suppress the replication of herpes simplex virus type 1 (HSV-1), an archetypal member of the alphaherpesvirus subfamily, and the molecular mechanism underneath is still illusive.Moreover, ectopic expression of hZAP inhibited the replication of R2621 but not WT HSV-1.HSV-1 UL41 was shown for the first time to evade the antiviral function of hZAP via its RNase activity.

View Article: PubMed Central - PubMed

Affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China. such1986@aliyun.com.

ABSTRACT

Background: The zinc finger antiviral protein (ZAP) is a host restriction factor that inhibits the replication of various viruses by degradation of certain viral mRNA. However, previous study demonstrated that ectopic expression of rat ZAP did not suppress the replication of herpes simplex virus type 1 (HSV-1), an archetypal member of the alphaherpesvirus subfamily, and the molecular mechanism underneath is still illusive.

Results: Human ZAP (hZAP) does not suppress the replication of herpes simplex virus 1, and HSV-1 UL41 protein was identified as an antagonist of hZAP by degrading its mRNA. Infection of wild-type (WT), but not UL41- mutant (R2621) virus, diminished the accumulation of hZAP to abrogate its antiviral activity. Moreover, ectopic expression of hZAP inhibited the replication of R2621 but not WT HSV-1.

Conclusion: HSV-1 UL41 was shown for the first time to evade the antiviral function of hZAP via its RNase activity.

Show MeSH
Related in: MedlinePlus