Hepatitis C Virus NS2 Protein Suppresses RNA Interference in Cells
RNAi interference (RNAi) is an evolutionarily conserved post-transcriptional gene silencing mechanism and has been well recognized as an important antiviral immunity in eukaryotes. Numerous viruses have been shown to encode viral suppressors of RNAi (VSRs) to antagonize antiviral RNAi. Hepatitis C virus (HCV) is a medically important human pathogen that causes acute and chronic hepatitis. In this study, we screened all the nonstructural proteins of HCV and found that HCV NS2 could suppress RNAi induced either by small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in mammalian cells. Moreover, we demonstrated that NS2 could suppress RNAi via its direct interaction with double-stranded RNAs (dsRNAs) and siRNAs, and further identified that the cysteine 184 of NS2 is required for the RNAi suppression activity through a serial of point mutation analyses. Together, our findings uncovered that HCV NS2 can act as a VSR in vitro, thereby providing novel insights into the life cycle and virus-host interactions of HCV.
KeywordsHepatitis C virus (HCV) NS2 Antiviral RNAi Viral suppressor of RNAi (VSR)
We wish to thank Prof. Ying Zhu (Wuhan, China) and Prof. Bryan Cullen (Durham, USA) for kindly providing materials. This work was supported by the Strategic Priority Research Program of Chinese Academy of Sciences (XDB29010300 to X.Z.), the National Natural Science Foundation of China (81873964 to Y.Q., 31670161 to X.Z. and 31800140 to J.M.), the Science and Technology Bureau of Wuhan (2018060401011309 to X.Z.), and the Advanced Customer Cultivation Project of Wuhan National Biosafety Laboratory (2018ACCP-MS11 to Y.Q.). X.Z. is supported by the Newton Advanced Fellowship from the Academy of Medical Sciences, UK (NAF005\1002).
HZ performed the experiments, analyzed the data and drafted the manuscript; QQ, TS, JX, JK and JM helped to perform the experiments; QQ and TS helped to analyze the data; YQ and XZ designed the experiments, analyzed the data, and finalized the manuscript. All authors approved the final manuscript.
Compliance with Ethics Standards
Conflict of interest
The authors declare that there are no conflict of interest.
Animal and Human Rights Statement
This article does not contain any studies with human or animal subjects performed by any of the authors.
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