The Mechanisms Of Long Noncoding RNA ITPRIP-1 Promoting Innate Immune Response

With the development of bioinformatics and technology,emerging evidence indicates that long non-coding RNAs(lncRNAs)regulate various biological processes,especially innate and adaptive immunity.However,the relationship between lncRNAs and viral infection remains largely unknown.Hepatitis C virus infection ca uses a global health issue.Over the past decade,plenty of antivirals against HCV have been developed to combat the disease to an appreciable extent,yet there is still no available vaccine.Hence,it is urgent to unveil the underlying mechanisms between HCV and host factors.In this study,we investigated the association between lncRNA ITPRIP-1 and viral infection and found out one target gene,MDA5.Firstly,we observed that lncITPRIP-1 was upregulated upon IFN stimulation and viral infection,it could i nhibit HCV replication in human hepatocytes.Secondly,further study demonstrated that lncITPRIP-1 promoted innate immune response via MDA5.Finally,we validated that lncITPRIP-1 possessed the ability to boost MDA5 oligomerization but exhibited no direct regulatory effects on MDA5 expression.Strikingly,we also found that MDA5 could be induced by HCV infection and suppress HCV replication independent of IFN signaling by binding to HCV RNA through its C-terminal deficient domain,in which lncITPRIP-1 played as an assistant,suggesting that lncITPRIP-1 might function as a cofactor of MDA5.Our study discovers the first lncRNA involved in MDA5 activation and reveals dual mechanisms of lncITPRIP-1 repressing HCV infection that lncITPRIP-1 enhances innate immune response through promoting the antiviral activity of MDA5 in both IFN-dependent and IFN-independent manner.Meanwhile,our work validates the essential role of MDA5 in IFN signaling and HCV infection,which may shed light on MDA5 function study and the treatment for hepatitis C patients.