鸡STING通过SLQxSyS-box调控IRF7机制研究

我们前期在鸡细胞中发现了一条特殊的RNA病毒识别通路“chMDA5-chSTING-IFNβ”，并确认chSTING通过chIRF7激活IFNβ。然而，chSTING激活chIRF7的机制尚不清楚。进一步研究发现，chSTING和chIRF7均具有保守的SLQxSyS-box基序，并且chSTING该基序内的S366能发生磷酸化并通过未知机制激活chIRF7。本项目拟通过研究，明确SLQxSyS-box在chSTING与chIRF7互作中的作用，确定chSTING该基序内S366磷酸化依赖的蛋白激酶，并通过验证提出的S366磷酸化“增强chSTING和chIRF7互作”和“促进chIRF7与chSTING解离”假说，阐明chSTING S366通过磷酸化调控chIRF7激活的具体方式，最终揭示chSTING调控chIRF7的重要机制，为利用家禽天然免疫力防控RNA病毒奠定理论和应用基础。

In previous study, we identified a special RNA virus recognition pathway chMDA5-chSTING-IFNβ in chicken cells, in which IFNβ is activated by chSTING through chIRF7. However, the mechanism of how chSTING activates chIRF7 remains unclear. Further studies showed that the SLQxSyS-box which is contained in both chSTING and chIRF7, is critical for chIRF7 activation by chSTING. S366 in chSTING SLQxSyS-box can be phosphorylated and may active chIRF7 by unknown mechanisms. In this project, the effects of SLQxSyS-box in the interaction between chSTING and chIRF7 will be verified, and the phosphorylation dependent protein kinases which phosphorylate S366 will be identified. In order to elucidate the specific manner of how chSTING activating chIRF7 is regulated by S366 phosphorylation, the hypothesis of S366 will enhance the interaction and promote the dissociation will be tested. Consequently the important mechanisms of chIRF7 regulation by chSTING will be revealed, which will improve the understanding of chicken innate immune system to prevent and control RNA virus infection.