Expression of Alphavirus Nonstructural Protein 2 (nsP2) in Mosquito Cells Inhibits Viral RNA Replication in Both a Protease Activity-Dependent and -Independent Manner.
Expression of Alphavirus Nonstructural Protein 2 (nsP2) in Mosquito Cells Inhibits Viral RNA Replication in Both a Protease Activity-Dependent and -Independent Manner.
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甲型病毒非结构蛋白2(NsP2)在蚊虫细胞中的表达可抑制病毒RNA的复制，其抑制作用依赖于蛋白水解酶活性，也不依赖于蛋白水解酶活性。
DOI：
10.3390/v14061327
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发表时间：
2022-06-17
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
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甲病毒是正链RNA病毒，主要由蚊子传播。被甲病毒感染的细胞由于在RNA复制水平上发生的阻断而对重复感染产生抗性。甲病毒复制蛋白，称为nsP 1 -4，是由非结构性多蛋白前体产生的，由nsP 2的蛋白酶活性加工而成。利用反式复制酶系统和复制子载体研究了基孔肯雅病毒和辛德毕斯病毒nsP 2对甲病毒RNA在蚊细胞中复制的影响。共表达的野生型nsP 2降低了同源病毒的RNA复制酶活性;这种效应被降低，但通常不会被nsP 2的蛋白酶活性位点的突变所消除。复制酶多聚蛋白中的突变阻断了nsP 2的切割，降低了nsP 2共表达的负面影响，证实nsP 2介导的RNA复制酶活性抑制主要是由于nsP 2介导的非结构多聚蛋白的加工。nsP 2的共表达还抑制异源甲病毒的复制酶的活性。因此，nsP 2的存在以蛋白酶活性依赖性和非依赖性方式抑制甲病毒RNA复制酶的形成和活性。这些知识提高了我们对甲病毒双重感染排除机制的理解，并可能有助于开发抗甲病毒方法。
Alphaviruses are positive-strand RNA viruses, mostly being mosquito-transmitted. Cells infected by an alphavirus become resistant to superinfection due to a block that occurs at the level of RNA replication. Alphavirus replication proteins, called nsP1-4, are produced from nonstructural polyprotein precursors, processed by the protease activity of nsP2. Trans-replicase systems and replicon vectors were used to study effects of nsP2 of chikungunya virus and Sindbis virus on alphavirus RNA replication in mosquito cells. Co-expressed wild-type nsP2 reduced RNA replicase activity of homologous virus; this effect was reduced but typically not abolished by mutation in the protease active site of nsP2. Mutations in the replicase polyprotein that blocked its cleavage by nsP2 reduced the negative effect of nsP2 co-expression, confirming that nsP2-mediated inhibition of RNA replicase activity is largely due to nsP2-mediated processing of the nonstructural polyprotein. Co-expression of nsP2 also suppressed the activity of replicases of heterologous alphaviruses. Thus, the presence of nsP2 inhibits formation and activity of alphavirus RNA replicase in protease activity-dependent and -independent manners. This knowledge improves our understanding about mechanisms of superinfection exclusion for alphaviruses and may aid the development of anti-alphavirus approaches.
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DOI：
10.1073/pnas.1900656116
发表时间：
2019-05-07
影响因子：
11.1
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影响因子：
5.9
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