Study On Role Of RUNX1 In Influenza A Virus H1N1 Infection

Influenza A virus belongs to the orthomyxoviridae family,which is a segmented,single-stranded,negative stranded RNA virus.Influenza A virus targets respiratory epithelial cells and uses host cells to replicate and spread,causing respiratory and pulmonary diseases.The innate immune system of the host is the first line of defense formed in the long-term evolution of the organism to receive the signal of infection from external pathogenic microorganisms and to clear the pathogen.The innate immune system is not only crucial to the initial recognition of the invading virus,but also can trigger a critical immune response to limit the replication of the virus.Like many other viruses,influenza viruses have evolved various strategies to escape their innate immunity.The RUNX family consists of RUNX1,RUNX2 and RUNX3.RUNX1 is a key transcription factor that regulates the expression of various inflammatory cytokines and chemokines and,and is capable of synergistically activating gene transcription by other transcription factors.Recent studies have shown that RUNX3 in RUNX family proteins is an important transcription factor that mediates the apoptosis of host epithelial cells induced by influenza A virus.Since RUNX1 and RUNX3 share a common binding domain Runt,we speculate that RUNX1 may also play an important role in influenza A virus infection.This study first explored the expression changes of RUNX1 in influenza A virus H1N1 infection.During the early stage of influenza A virus H1N1 infection,the mRNA and protein expressions of RUNX1 were significantly induced,and the expression levels were positively correlated with the time of infection and virulence.Second,we investigated the effect of RUNX 1 on the replication of influenza A virus in A549.The overexpression of RUNX1 in A549 cells significantly promoted the replication of H1N1,whereas the downregulation of RUNX1 inhibited the replication of the virus.Finally,this study explored the role and mechanism of RUNX1 in host innate immunity induced by influenza A virus HIN1 infection.We found that the overexpression of RUNX1 in A549 cells inhibited the expression of IAV-induced IRF3 and STAT1 proteins,leading to the downregulation of mRNA levels of IFN interferon stimulating genes(ISGs).Conversely,the knockdown of RUNX1 significantly promoted the expression of IRF3 and STAT1,thereby promoting the innate antiviral response of the host.In summary,this study is the first to reveal the role of host protein RUNX1 in influenza A virus H1N1 infection and to elucidate the relevant mechanisms:1)Influenza A virus H1N1 infection specifically induces the expression of host protein RUNX1.2)RUNX1 is involved in the regulation of IFN signaling pathway mediated by influenza A virus H1N1 infection,affecting the release of the IFN signaling of type I interferon and antiviral protein MxA and ISG15.3)The high expression of RUNX1 induced by influenza a virus H1N1 infection inhibits the expression of IRF3 and STAT1,thereby inhibiting the interferon signaling pathway to help the virus replicate.This study helps to clarify the role and mechanism of host protein RUNX1 in influenza A virus HIN1 infection,and provides an important theoretical basis for clinical prevention of influenza A virus infection and the development of antiviral drugs.