IRF7 Is Involved in Both STING and MAVS Mediating IFN- beta Signaling in IRF3-Lacking Chickens

文献类型： 外文期刊

第一作者： Cheng, Yuqiang

作者： Cheng, Yuqiang;Zhu, Wenxian;Niu, Qiaona;Wang, Hengan;Yan, Yaxian;Sun, Jianhe;Ding, Chan

作者机构：

期刊名称：JOURNAL OF IMMUNOLOGY （ 影响因子：5.422； 五年影响因子：6.029 ）

ISSN： 0022-1767

年卷期： 2019 年 203 卷 7 期

页码：

收录情况： SCI

摘要： IFN regulatory factor (IRF) 3 has been identified as the most critical regulator of both RNA and DNA virus-induced IFN production in mammals. However, ambiguity exists in research on chicken IRF5; in particular IRF3 seems to be missing in chickens, making IFN regulation in chickens unclear. In this study, we comprehensively investigated the potential IFN-related IRFs in chickens and showed that IRF7 is the most critical IFN-beta regulator in chickens. With a chicken IRF7 (chIRF7) knockout DF-1 cell line, we conducted a series of experiments to demonstrate that chIRF7 is involved in both chicken STING (chSTING)- and chicken MAVS (chMAVS)-mediated IFN-beta regulation in response to DNA and RNA viral infections, respectively. We further examined the mechanisms of chIRF7 activation by chSTING. We found that chicken TBK1 (chTBK1) is indispensable for chIRF7 activation by chSTING as well as that chSTING interacts with both chIRF7 and chTBK1 to function as a scaffold in chIRF7 activation by chTBK1. More interestingly, we discovered that chSTING mediates the activation of chIRF7 through a conserved SLQxSyS motif. In short, we confirmed that although IRF3 is missing in chickens, they employ IRF7 to reconstitute corresponding IFN signaling to respond to both DNA and RNA viral infections. Additionally, we uncovered a mechanism of chIRF7 activation by chSTING. The results will enrich and deepen our understanding of the regulatory mechanisms of the chicken IFN system.

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