ISG20 inhibits bluetongue virus replication

Di Kang; Shandian Gao; Zhancheng Tian; Guorui Zhang; Guiquan Guan; Guangyuan Liu; Jianxun Luo; Junzheng Du; Hong Yin

doi:10.1016/j.virs.2022.04.010

August 2022

Di Kang, Shandian Gao, Zhancheng Tian, Guorui Zhang, Guiquan Guan, Guangyuan Liu, Jianxun Luo, Junzheng Du and Hong Yin. ISG20 inhibits bluetongue virus replication[J]. Virologica Sinica, 2022, 37(4): 521-530. doi: 10.1016/j.virs.2022.04.010

Citation: Di Kang, Shandian Gao, Zhancheng Tian, Guorui Zhang, Guiquan Guan, Guangyuan Liu, Jianxun Luo, Junzheng Du, Hong Yin. ISG20 inhibits bluetongue virus replication .VIROLOGICA SINICA, 2022, 37(4) : 521-530. http://dx.doi.org/10.1016/j.virs.2022.04.010

ISG20抑制蓝舌病毒的复制

康棣 ^a ,
高闪电 ^a ,
田占成 ^a ,
张国芮 ^a ,
关贵全 ^a ,
刘光远 ^a ,
罗建勋 ^a ,
独军政 ^a,, ,
殷宏 ^a,b,,

中国农业科学院兰州兽医研究所

通讯作者： 独军政, dujunzheng@caas.cn; 殷宏, yinhong@caas.cn
收稿日期： 2021-08-29
录用日期： 2022-04-22

摘要

ISG20是一种由干扰素诱导的能够抑制病毒复制的核酸外切酶，尽管人们认为ISG20能够降解病毒RNA，但是其对不同病毒的具体作用机理目前尚不明确。本研究聚焦于羊ISG20（oISG20）在蓝舌病毒（BTV）感染细胞中的作用机理，研究发现BTV感染细胞后显著上调oISG20基因的转录水平，且与BTV感染时间和感染剂量呈正相关。在MDOK细胞中过表达oISG20后，BTV在基因水平、病毒蛋白的表达及病毒滴度均明显下降，相反，在敲低oISG20基因的表达后，BTV复制水平明显升高，发现oISG20蛋白能够与BTV VP4蛋白发生互作，核酸外切酶失活的突变型oISG20抑制BTV复制的能力降低，此时突变型oISG20与VP4蛋白的相互作用减弱，提示oISG20与VP4蛋白的相互作用与其抑制BTV的复制相关。本研究明确了oISG20在BTV复制过程的作用，并为深入研究ISG20抑制双链RNA病毒复制的作用机理奠定了基础。
- 蓝舌病毒
- , 干扰素刺激基因
- , 羊ISG20
- , 病毒复制
- , 抗病毒免疫

ISG20 inhibits bluetongue virus replication

a State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China;

Corresponding author: Junzheng Du, dujunzheng@caas.cn Hong Yin, yinhong@caas.cn
Received Date: 29 August 2021
Accepted Date: 22 April 2022

Abstract

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 upregulated 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.
- Bluetongue virus (BTV)
- , Interferon-stimulated genes (ISGs)
- , Ovine ISG20
- , Virus replication
- , Antiviral immunity

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Electronic Supplementary Material

10.1016j.virs.2022.04.010-ESM.docx