The Role And Mechanism Of PZR In The Innate Immune Response To Viral Infection

PZR(protein zero-related)belongs to the immunoglobulin family and is a transmembrane glycoprotein.From the discovery of PZR to structural studies and functional explorations,the existing research shows that PZR affects the metastasis of various cancer cells such as hepatocellular carcinoma,gallbladder cancer,ovarian cancer,and breast cancer,which in turn affects the progression of cancer,as well as Noonan syndrome and LEOPARD.One of the targets of the syndrome affects its pathogenesis,and there is no relevant research on the influence of PZR on innate immunity.This study focuses on exploring the relationship between PZR and innate immune response to viral infection.First,we found through Western blotting that the protein level of PZR was significantly reduced in Huh7 cells upon VSV(Vesicular stomatitis virus)or NDV(Newcastle disease virus)infection.Next,Real-time fluorescence quantitative PCR showed that PZR inhibited the induction of IFNs and ISGs by long-chain poly(I:C),HCV 3'UTR,VSV or NDV.Further western blotting showed that silencing PZR enhanced the phosphorylation of IRF3(Interferon regulatory Factor 3)and STAT1(Signal transducer and activator of transcription 1)activated by VSV or NDV.All these data supported that PZR inhibits the innate immune response to RNA viral infection.In addition,We found that PZR interacted with the TM domain of the MAVS(Mitochondrial antiviral signaling protein)with the help of co-immunoprecipitation.We found that PZR has a negative regulatory effect on the innate immune response to RNA viruses and PZR may regulate the innate immunity by targeting MAVS.It is hoped that,new ideas will be added to the regulation of innate immunity by PZR.