Molecular Mechanism Of BST2 Inhibition Porcine Epidemic Diarrhea Virus Replication By Targeting And Degrading Virus Nucleocapsid Protein

Porcine epidemic diarrhea virus(PEDV)is one of the most important pathogens in swine industry,which caused a great harm to world pig industry.The innate immunity restriction factor BST2(bone marrow stromal cell antigen 2)inhibits viral replication by tethering enveloped virions to the cell surface to restrict viral release and by inducing the NFKB-dependent antiviral immune response.In our previous research,we found that BST2 significantly inhibited the proliferation of PEDV.The molecular mechanism of the BST2 inhibiting PEDV proliferation is not clear.This project will use chromatin immunoprecipitation and luciferase reporter assay to screen and verify the transcription factors involved in the regulation of BST-2 expression,to analyze the mechanism of the regulation of BST-2 expression after viral infection.Using protein degradation pathway inhibitors and RNA interference to analysis the molecular mechanism of BST2 promoting the degradation of N protein to inhibit viral multiplication.Results presented in this study can be summarized as follows:1.Host cells directly up-regulated the expression of IRF1 independent of the IFN signaling pathway,and the IRF1 plays a direct role in inducing BST2 expression by binding to the BST2 promoter.2.BST2 significantly inhibited the proliferation of PEDV.BST2 recruits MARCHF8 to catalyze the ubiquitination of the PEDV N protein.The ubiquitinated N protein is then recognized by CALCOCO2/NDP52,which delivers it to autolysosome for degradation through the selective autophagy pathway.