Functional Research Of HRIK In Innate Immune Signaling

Antiviral innate immune system is critical for protecting organism from viral infection.Cells detect DNA or RNA viruses through pattern recognition receptors(PRRs).PRRs and associated STING/MAVS signaling pathways induce the production of type I interferons and cytokines to resist virus proliferation and release.Gammaherpesviruses are large double-stranded DNA viruses that result in many diseases.A mouse model has been previously developed for studying gammaherpesvirus pathogenesis by using murine gammaherpesvirus 68(MHV68).A high level expression of one unknown gene RIK was screened from MHV68 transformed B lymphoma cells.We next found homologous human RIK(hRIK)gene by BLAST and constructed plasmids.Mass spectrometry analyses show potential interaction between hRIK and innate immune proteins.Therefore,we hypothesized that hRIK is an antiviral innate immune protein.In this study,we found that hRIK which was localized in ER induced the production of type I interferons and cytokines.hRIK also interacted with many innate immune proteins by co-imunoprecipitation analyses.Besides,hRIK contained an N-terminal leucine-rich domain which was essential for interaction with innate immune proteins.Moreover,mutant hRIK-L induced more type I interferons than wide type hRIK.Due to the important role of hRIK played in regulating innate immune system,its mechanism of antivirus needs to be further studied.