Mechanisms In Porcine E3 Ubiquitin Ligase RNF122 Mediates Immune Escape Of Porcine Reproductive And Respiratory Syndrome Virus Infection

Porcine reproductive and respiratory syndrome(PRRS)is an immunosuppressive disease caused by porcine reproductive and respiratory syndrome virus(PRRSV),which is a serious threat to the global pig industry.At present,there is no vaccine or drug that can effectively prevent and cure this disease,and further research is needed on the specific molecular mechanism of the interaction between PRRSV infection and host cells.In this study,we identified a porcine E3 ubiquitin ligase RNF122,mined the key proteins encoded by PRRSV and IFN signaling pathway interacting with RNF122,and explored the molecular mechanism of RNF122 in PRRSV infection and immunity.The main research results are as follows:1.Porcine E3 ubiquitin ligase RNF122 plays an important role in PRRSV infection.The role of E3 ubiquitin ligase RNF122 in the process of PRRSV infection was confirmed by the findings that PRRSV can promote the expression of RNF122 and RNF122 can promote the replication of PRRSV.2.PRRSV promotes the expression of RNF122 by mediating the transcriptional regulation of RNF122.The core promoter region of RNF122 was identified,and HLTF and E2 F complexe were selected as the key transcription factors binding to the core promoter region.It was demonstrated that PRRSV could regulate transcription factor HTLF by encoding nsp1α and nsp7,and regulate transcription factor E2 F complex by encoding nsp9,so as to further regulate the transcription activity of RNF122 and promote the expression of RNF122.3.RNF122 promotes PRRSV proliferation through multiple ubiquitination.RNF122 was found to be able to ubiquitinate the nsp4 encoded by PRRSV at the K63 position to maintain protein stability and promote viral replication.RNF122 mediated ubiquitination at K27 and K48 of MDA5,negatively regulating the type I interferon pathway.The mechanism by which E3 ubiquitin ligase RNF122 multi-ubiquitination regulates PRRSV proliferation was clarified.In conclusion,our study proposed a new mechanism of PRRSV using E3 ubiquitin ligase to maintain its stability in the body from the perspective that the virus regulates the expression of E3 ubiquitin ligase in the body to antagonize IFN and promote viral replication,which provides a new idea for PRRSV prevention and control.