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 enc...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 doublestranded 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.展开更多
基金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.)+2 种基金the Science and Technology Bureau of Wuhan(2018060401011309 to X.Z.)the Advanced Customer Cultivation Project of Wuhan National Biosafety Laboratory(2018ACCP-MS11 to Y.Q.)supported by the Newton Advanced Fellowship from the Academy of Medical Sciences,UK(NAF005\1002)。
文摘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 doublestranded 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.
