SLC15A3 Participates MAVS-mediated Anti-RNA Viral Natural Immune Response

As the largest group of viruses,RNA viruses have always brought severe challenges to human health.The innate immune system relies primarily on the Toll-like receptor 3(TLR3)on the endosome and the RIG-I-like receptor(RLRs)located in the cytoplasm to recognize and respond to RNA viruses.The interaction of RLRs with the mitochondrial antiviral signaling protein(MAVS)activates the interferon regulatory factor 3(IRF3)and nuclear factor-κB(NF-κB),thereby synergistically inducing the expression of type I interferon and inflamatory factors,which play an important role in antiviral innate immunity.solute carrier family 15 member 3(SLC15A3)has been reported that SLC15A3 can inhibit the invasion of various bacteria and viruses,such as bacterial muramyl dipeptide(MDP),chikungunya virus(CHIKV)and herpes simplex virus 1(HSV-1)and so on.At present,there are no reports on the molecular mechanism of SLC15A3 antiviral natural immunity.vesicular stomatitis virus(VSV)belongs to the enveloped virus and invades the host cytoplasm through the endosome pathway;Sendai Virus(Se V)invades the cells by directly merging with the cell membrane without passing through the endosomes,so we use the ds RNA nucleic acid mimetic Poly(I:C),VSV,Se V as stimuli to explore SLC15A3 mediated by RLRs the role of type I interferon in antiviral innate immunity.Our study found that SLC15A3 not only inhibits RNA virus replication in vivo,but also binds to the antiviral signaling protein MAVS,activates phosphorylation of the downstream transcription factor IRF3,positively regulates RLRs-mediated signaling pathways that produce type I intergeron to anti-RNA viruses.We not only reveal the natural immune regulation mechanism of SLC15A3 anti-RNA virus,but also provide theoretical guidance for the treament of infectious diseases of RNA virus.