IRF8 在抗DNA病毒天然免疫应答中的作用和机制研究

抗病毒天然免疫反应是机体抵抗病毒感染和清除已感染细胞的重要手段，其发生和调控的分子机制研究是过去十多年生命科学领域的研究热点。干扰素调节因子家族成员IRF3和IRF7是在抗病毒免疫应中调控I型干扰素表达的关键蛋白，然而对于其它IRFs在此过程中的作用了解得还不是很清楚。在前期的研究中，我们鉴定IRF8在抗DNA病毒免疫应答中具有重要作用。我们发现敲低或敲除IRF8的表达显著抑制DNA病毒而不是RNA病毒诱导的下游信号。而且，IRF8能与MITA相互作用，他们的相互作用随着HSV-1的刺激而增强。此外，HSV-1能诱导IRF8入核和发生降解。基于这些发现，我们将进一步阐明IRF8调控抗DNA病毒免疫应答的具体分子机制，并揭示泛素化、磷酸化等修饰在IRF8激活调控中的作用。我们的研究将揭示MITA-IRF8介导的抗DNA病毒免疫应答的新途径。

The antiviral innate immune response is critical for the host to eliminate invaded viruses and remove infected cells. How the host initiates efficient innate immune response after viral infection and how the immune response is controlled are key questions in the past years. Interferon regulatory factor 3 (IRF3) and IRF7 are critical regulators for the induction of type I interferon (IFN-I) in antiviral innate immunity, but little is known about the roles of other IRFs in antiviral innate immunity. In previous studies, we have identified that IRF8 plays an important role in innate immune response to DNA virus. We observed that knockdown or knockout of IRF8 significantly inhibited DNA-virus- but not RNA-virus-induced innate immune responses. Meanwhile, IRF8 interacted with MITA and their interaction was enhanced after HSV-1 infection. In addition, IRF8 was transported into the nuclear from cytoplasm and was degraded during HSV-1 infection. Based on these findings, we will further elucidate the molecular mechanisms of IRF8-mediated regulation of DNA virus-induced signaling and reveal the roles of ubiquitylation and phosphorylation in the regulation of IRF8 activation. Our research will provide important insights into an unrecognized MITA-IRF8-mediated signaling pathway of innate immune responses to DNA viruses.