State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
Virol Sin. 2022 Aug;37(4):521-530. doi: 10.1016/j.virs.2022.04.010. Epub 2022 May 2.
ISG20 is an interferon-inducible exonuclease that inhibits virus replication. Although ISG20 is thought to degrade viral RNA, the antiviral mechanism and specificity of ISG20 remain unclear. In this study, the antiviral role of ovine ISG20 (oISG20) in bluetongue virus (BTV) infection was investigated. It was found that BTV infection up-regulated the transcription of ovine ISG20 (oISG20) in a time- and BTV multiplicity of infection (MOI)-dependent manner. Overexpression of oISG20 suppressed the production of BTV genome, proteins, and virus titer, whereas the knockdown of oISG20 increased viral replication. oISG20 was found to co-localize with BTV proteins VP4, VP5, VP6, and NS2, but only directly interacted with VP4. Exonuclease defective oISG20 significantly decreased the inhibitory effect on BTV replication. In addition, the interaction of mutant oISG20 and VP4 was weakened, suggesting that binding to VP4 was associated with the inhibition of BTV replication. The present data characterized the anti-BTV effect of oISG20, and provides a novel clue for further exploring the inhibition mechanism of double-stranded RNA virus by ISG20.
ISG20 是一种干扰素诱导的核酸外切酶,可抑制病毒复制。虽然 ISG20 被认为能降解病毒 RNA,但 ISG20 的抗病毒机制和特异性仍不清楚。本研究探讨了绵羊 ISG20(oISG20)在蓝舌病毒(BTV)感染中的抗病毒作用。结果发现,BTV 感染以时间和 BTV 感染复数(MOI)依赖的方式上调 oISG20 的转录。oISG20 的过表达抑制了 BTV 基因组、蛋白和病毒滴度的产生,而 oISG20 的敲低则增加了病毒复制。发现 oISG20 与 BTV 蛋白 VP4、VP5、VP6 和 NS2 共定位,但仅与 VP4 直接相互作用。无核酸外切酶活性的 oISG20 显著降低了对 BTV 复制的抑制作用。此外,突变 oISG20 与 VP4 的相互作用减弱,表明与 VP4 的结合与抑制 BTV 复制有关。本研究数据表征了 oISG20 抗 BTV 的作用,为进一步探索 ISG20 抑制双链 RNA 病毒的机制提供了新线索。