Elucidation of the mechanism underlying core histone-mediated antiviral innate immune response

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Previous our research has clarified that H2B could sense viral double stranded DNA (dsDNA), and induce antiviral innate immune response. The goal of current research is to elucidate molecular mechanism of H2B-mediated recognition of cytoplasmic DNA.The results showed that extranuclear H2B interacts with IPS-1 upon sensing cytoplasmic DNA. We also identified the novel adaptor molecule, named as CIAO, to connect H2B with IPS-1, and showed that H2B-CIAO-IPS-1 complex has an important role to induce type I IFNs upon antiviral innate immune response. Furthermore, chimera protein N'-CARD, that is constructed by fusion of H2B fragment to IPS-1 fragment, could induce strong type I IFNs production, suggesting that H2B-CIAO-IPS-1 complex could be useful target to develop the novel immunomodulating drugs.