Gene silencing (RNA silencing) plays a fundamental role in antiviral defense in plants, fungi and invertebrates. Viruses encode proteins that suppress gene silencing to counter host defense. Viral suppressors of RNA s...Gene silencing (RNA silencing) plays a fundamental role in antiviral defense in plants, fungi and invertebrates. Viruses encode proteins that suppress gene silencing to counter host defense. Viral suppressors of RNA silencing (VSRs) have been identified from almost all plant virus genera and some viruses of insects and mammals. Recent studies have revealed that VSRs counter host defense and interfere with host gene regulation by interacting with RNA or important components of the RNA silencing pathway. Here, we review the current understanding of the complex mechanisms of VSRs that have been revealed by recent studies.展开更多
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 National Basic Research Program of China (Grant No. 2012CB114004)the National Natural Science Foundation of China (Grant Nos. 31030005 and 30910103904)
文摘Gene silencing (RNA silencing) plays a fundamental role in antiviral defense in plants, fungi and invertebrates. Viruses encode proteins that suppress gene silencing to counter host defense. Viral suppressors of RNA silencing (VSRs) have been identified from almost all plant virus genera and some viruses of insects and mammals. Recent studies have revealed that VSRs counter host defense and interfere with host gene regulation by interacting with RNA or important components of the RNA silencing pathway. Here, we review the current understanding of the complex mechanisms of VSRs that have been revealed by recent studies.
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.
