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

我们以前的研究已经阐明，H2B可以感知病毒双链DNA(DsDNA)，并诱导抗病毒先天免疫反应。目前的研究目标是阐明H_2B介导的胞质DNA识别的分子机制。结果表明，核外的H_2B与IPS-1相互作用，感应到胞质DNA。我们还鉴定了连接H_2B和IPS-1的新型接头分子CIAO，并表明H_2B-CIAO-IPS-1复合体在诱导I型IFN抗病毒先天免疫反应中具有重要作用。此外，通过将H_2B片段与IPS-1片段融合构建的嵌合体蛋白N‘-CARD能诱导较强的I型IFN的产生，提示H_2B-Ciao-IPS-1复合体可能是开发新型免疫调节药物的有用靶点。

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.