FIP200 restricts RNA virus infection by facilitating RIG-I activation.
FIP200 restricts RNA virus infection by facilitating RIG-I activation.
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DOI：
10.1038/s42003-021-02450-1
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发表时间：
2021-07-29
影响因子：
5.9
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Wang L;Song K;Hao W;Wu Y;Patil G;Hua F;Sun Y;Huang C;Ritchey J;Jones C;Liu L;Guan JL;Li S
视黄酸诱导基因I（RIG-I）感知病毒RNA并引发先天免疫信号级联以诱导I型干扰素表达。目前，控制RIG-I激活的调节机制仍有待充分阐明。在这里，我们表明，FAK家族激酶相互作用蛋白200 kDa（FIP 200）促进RIG-I激活。FIP 200缺陷损害RIG-I信号传导并增加宿主对RNA病毒感染的易感性。体内研究进一步证明，由于先天免疫应答降低，FIP 200敲除小鼠更容易受到RNA病毒感染。机制研究表明，FIP 200与RIG-I的解旋酶结构域竞争与两个串联的半胱天冬酶激活和募集结构域（2CARD）的相互作用，从而促进2CARD从抑制状态释放。此外，FIP 200形成二聚体并促进2CARD寡聚化，从而促进RIG-I活化。综上所述，我们的研究将FIP 200定义为正调节RIG-I激活的先天免疫信号分子。Lingyan Wang等人报告称，自噬相关蛋白FIP 200与RNA传感器RIG-I相互作用，触发I型干扰素途径的激活。
Retinoic acid-inducible gene I (RIG-I) senses viral RNA and instigates an innate immune signaling cascade to induce type I interferon expression. Currently, the regulatory mechanisms controlling RIG-I activation remain to be fully elucidated. Here we show that the FAK family kinase-interacting protein of 200 kDa (FIP200) facilitates RIG-I activation. FIP200 deficiency impaired RIG-I signaling and increased host susceptibility to RNA virus infection. In vivo studies further demonstrated FIP200 knockout mice were more susceptible to RNA virus infection due to the reduced innate immune response. Mechanistic studies revealed that FIP200 competed with the helicase domain of RIG-I for interaction with the two tandem caspase activation and recruitment domains (2CARD), thereby facilitating the release of 2CARD from the suppression status. Furthermore, FIP200 formed a dimer and facilitated 2CARD oligomerization, thereby promoting RIG-I activation. Taken together, our study defines FIP200 as an innate immune signaling molecule that positively regulates RIG-I activation. Lingyan Wang et al. report that the autophagy-associated protein FIP200 interacts with the RNA sensor RIG-I to trigger activation of the type I interferon pathway.
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