Mechanism Of Immune Responses Of Host Cells Induced By Peste Des Petits Ruminants Virus

Peste des petits ruminants disease(PPR)is a highly contagious,and immunosuppressive small ruminants disease caused by PPR virus(PPRV),with the mortality of 50-80%.It is seriously monitored by Food and Agriculture Organization of the United Nations.PPRV inhibited interferon(IFN)responses seriously,but there was a lack of reports that were related to innate immune response induced by PPRV infection,selection of drugs against PPRV infection and developments of new antiviral pathway.From this study,we can get conclution:1.During PPRV evolution,synonymous codon usage patterns of different viral genes were influenced by mutation pressure of nucleotide composition and natural selection of host.The secondary structure of PPRV N protein was obviously influenced by synonymous codon usage patterns of N gene and translation speed of tRNA abundances of host.2.In this study,when PPRV invaded into HEK293 T cell line,IFN-β,IFN-λ2,IFN-λ3 and several interferon stimulation genes(ISG),such as ISG56,ISG15 and CXCL10,can be strongly induced.When exogenous IFN-alpha-2b and IFN-λ3 did with HEK293 T cell line,PPRV infection can be blocked.However,Jak-inhibitor which is an inhibitor blocking signal pathway induced by IFN did not inhibit production of IFN and other cytokines,but it was able to block immune response by exogenous IFN.3.Apart from autophage,the autophage-related(Atg)proteins take part in many physiological processes,such as viral replication,inflammatory immune response and so on.In the previous study,we studied for the roles of Atg proteins in the life cycle of viral infection,and found that Atg proteins can be activated and play important roles in regulating innate immunity system against viral infection.We get the conclution that Atg13 protein inhibits PPRV prolification by activating the signaling pathway of IFN-β.4.Ribavin and Mycophenolic are ribonucleoic analogs which have impact on IMPDH activities to stop GTP pool,which are used for antiviral infections.In this study,Ribavin and Mycophenolic had strong antiviral effect on PPRV infection.5.Furthermore,depending on CRISPR-cas9 mehtod,Vinculin protein was knocked out from Vero cell line.Although this Vero cell line which did not contain Vinculin gene had a low growth rate,this cell line represented an obvious resistance to PPRV replication.6.The two important IFNs were found during PPRV infection,the two effective antiviral drugs(Ribavirin and Mycophenolic)were primarily identified.These findings might give new strategies to perform resistance to PPRV infection to some cherish wild small ruminants,especially Tibetan antelope.Interestingly,Atg13 protein of HEK293 cell line had an important role in mediating immune signalling pathway of innate immune response,and Vinculin protein of Vero cell line functioned as antiviral response during PPRV replication.These findings give new insights into some proteins of host cell performing antiviral IIIfunctions during PPRV infection,at the same time;provide novel ideas for preventing and controlling PPR.