Study On Antagonism Of Bovine Rotavirus NSP3 Against Type Ⅰ Interferon

Bovine Rotavirus(BRV)is the main viral pathogen causing diarrhoeal disease in cattle,mostly infecting calves under 1 month of age and causing serious economic losses to the cattle industry.The mature viral particle of BRV contains an 11-segment double-stranded RNA genome that encodes six structural and six non-structural proteins,with the nonstructural protein NSP3 playing an important role in the replication of the virus.Innate immunity is the body’s key defence system against viruses,and type I interferon is the main natural immune antiviral factor.In order to investigate the regulatory effect of BRV NSP3 protein on interferon,the bovine rotavirus HSX-21 strain,which was isolated in the pre-laboratory,was used as the subject of this experiment.At the molecular and protein levels,the study of NSP3 mediated type I interferon expression through both poly(I:C)and RIG-I.The results showed that BRV NSP3 protein down-regulated the transcription of IFN-β and ISGs m RNA mediated by poly(I:C)in a dose-dependent manner and showed significant inhibition at 800 ng(P<0.01).BRV NSP3 blocks the poly(I:C)-mediated type I interferon signalling pathway by inhibiting phosphorylation of IRF3 protein.In the RIG-I-mediated signalling pathway,BRV NSP3 significantly represses gene transcription of the key signalling molecules MAVS,IRF3.BRV NSP3 protein inhibits the expression of RIG,MAVS,TBK1,and IRF3,key proteins in the RIGI signaling pathway.The results of a dual-luciferase reporter gene assay targeting BRV NSP3,a key factor in the RIG-I signalling pathway,showed that BRV NSP3 antagonises type I interferon production by targeting TBK1 upstream of the RIG-I signalling pathway.In summary,it was shown that bovine rotavirus NSP3 has a significant antagonistic effect on type I interferon by mediating poly(I:C)and RIG-I.A the oretical basis for further research into the innate immunity of BRV escape hosts and for drug and vaccine design and development.