The Mechanism Of Rubella Virus Immune Evasion And The Regulation Of RNA Interference

RNA interference(RNAi)is a crucial antiviral defense mechanism in eukaryotes.In this process,several strategies have been adopted by viruses and host cells to counter each other.Based on the both sides,we investigated how Rubella virus(RuV)escaped the antiviral RNAi and the function of insect cofactors in mammals’ RNAi,respectively.RuV is the infectious agent of a series of birth defect diseases termed congenital rubella syndrome.In this study,we identified that RuV capsid protein is a potent VSR that can efficiently suppress sh RNA-and si RNA-induced RNAi in mammalian cells.Moreover,the VSR activity of RuV capsid is dependent on its dimerization and double-stranded RNA(ds RNA)-binding activity.Ectopic expression of RuV capsid can effectively rescue the replication defect of VSR-deficient virus.In addition,we designed a peptide FYR which could disrupt the dimerization and VSR activity of capsid and inhibit the replication of RuV in host cells.Together,our findings uncover that RuV encodes a VSR to evade antiviral RNAi response,which sheds light on the potential therapeutic target against RuV.Loquacious-PD(Loqs-PD)is a Dicer-2 partner protein in the fruit flies Drosophila melanogaster,promoting the production of both endogenous and exogenous si RNAs by increasing substrate affinity.In this study,we identified that Loqs-PD could enhance the antiviral activity of RNAi in mammalian cells.Loqs-PD could enhance the ds RNA-binding ability of Dicer by interacting with Dicer,which led to a increasing production of cleaved si RNA.Dengue virus(DENV)is a mosquito-borne flavivirus,causing dengue fever and dengue hemorrhagic fever.Enterovirus A71(EV-A71)is the main causative agent of hand-foot-and-mouth disease(HFMD).DENV and EV-A71 have emerged as the major global threats to public health.Ectopic expression of Loqs-PD could inhibit the replication of DENV and EV-A71 in cells.Furthermore,a significant amount of vsi RNA(virus-derived si RNA)could be detected by the RNA deep sequecing.In a word,our findings redefine that Loqs-PD can act as an enhancer of the antiviral RNAi in mammalian cells,which partially explains the differences of antiviral RNAi between insects and mammalian cells.