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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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HSV-1 UL41 protein promotes hZAP mRNA degradation. a 293Trex-hZAPL or 293Trex-hZAPS cells were transfected with pCMV-Flag control vector or increasing amount of UL41-Flag plasmid. At 6 h post-transfection, cells were mock treated or treated with tetracycline (1000 ng/mL) to induce hZAPL or hZAPS expression. Quantitative RT-PCR analysis was then performed to detect the mRNA level of hZAPL or hZAPS. b 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1 or R2621 at an MOI of 1 or 10, respectively. At 2 h post-infection, cells were mock treated or treated with tetracycline (1000 ng/mL). Quantitative RT-PCR analysis was then performed to detect the mRNA level of hZAPL or hZAPS. One representative of three independent experiments was shown. (*P < 0.05, **P < 0.01)
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Fig3: HSV-1 UL41 protein promotes hZAP mRNA degradation. a 293Trex-hZAPL or 293Trex-hZAPS cells were transfected with pCMV-Flag control vector or increasing amount of UL41-Flag plasmid. At 6 h post-transfection, cells were mock treated or treated with tetracycline (1000 ng/mL) to induce hZAPL or hZAPS expression. Quantitative RT-PCR analysis was then performed to detect the mRNA level of hZAPL or hZAPS. b 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1 or R2621 at an MOI of 1 or 10, respectively. At 2 h post-infection, cells were mock treated or treated with tetracycline (1000 ng/mL). Quantitative RT-PCR analysis was then performed to detect the mRNA level of hZAPL or hZAPS. One representative of three independent experiments was shown. (*P < 0.05, **P < 0.01)

Mentions: UL41 was an endoribonuclease with its substrate specificity similar to that of RNase A [15]. Therefore, we hypothesize that UL41 decreases hZAP expression via its RNase activity to degrade hZAP mRNA. To test this hypothesis, UL41-Flag plasmid was transfected into 293Trex-hZAPL and 293Trex-hZAPS cells, and cells were treated with tetracycline (1000 ng/mL) 6 h post-transfection. As a result, ectopic expression of UL41-Flag downregulated the abundance hZAPL and hZAPS mRNA in a dose dependent manner (Fig. 3a).Fig. 3


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)

HSV-1 UL41 protein promotes hZAP mRNA degradation. a 293Trex-hZAPL or 293Trex-hZAPS cells were transfected with pCMV-Flag control vector or increasing amount of UL41-Flag plasmid. At 6 h post-transfection, cells were mock treated or treated with tetracycline (1000 ng/mL) to induce hZAPL or hZAPS expression. Quantitative RT-PCR analysis was then performed to detect the mRNA level of hZAPL or hZAPS. b 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1 or R2621 at an MOI of 1 or 10, respectively. At 2 h post-infection, cells were mock treated or treated with tetracycline (1000 ng/mL). Quantitative RT-PCR analysis was then performed to detect the mRNA level of hZAPL or hZAPS. One representative of three independent experiments was shown. (*P < 0.05, **P < 0.01)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666169&req=5

Fig3: HSV-1 UL41 protein promotes hZAP mRNA degradation. a 293Trex-hZAPL or 293Trex-hZAPS cells were transfected with pCMV-Flag control vector or increasing amount of UL41-Flag plasmid. At 6 h post-transfection, cells were mock treated or treated with tetracycline (1000 ng/mL) to induce hZAPL or hZAPS expression. Quantitative RT-PCR analysis was then performed to detect the mRNA level of hZAPL or hZAPS. b 293Trex-hZAPL cells or 293Trex-hZAPS cells were infected with WT HSV-1 or R2621 at an MOI of 1 or 10, respectively. At 2 h post-infection, cells were mock treated or treated with tetracycline (1000 ng/mL). Quantitative RT-PCR analysis was then performed to detect the mRNA level of hZAPL or hZAPS. One representative of three independent experiments was shown. (*P < 0.05, **P < 0.01)
Mentions: UL41 was an endoribonuclease with its substrate specificity similar to that of RNase A [15]. Therefore, we hypothesize that UL41 decreases hZAP expression via its RNase activity to degrade hZAP mRNA. To test this hypothesis, UL41-Flag plasmid was transfected into 293Trex-hZAPL and 293Trex-hZAPS cells, and cells were treated with tetracycline (1000 ng/mL) 6 h post-transfection. As a result, ectopic expression of UL41-Flag downregulated the abundance hZAPL and hZAPS mRNA in a dose dependent manner (Fig. 3a).Fig. 3

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