FIP200 restricts RNA virus infection by facilitating RIG-I activation

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 200kDa (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.

Automated summary

FIP200 facilitates RIG-I activation, deficiency of which impairs RIG-I signaling and increases host susceptibility to RNA virus infection. The interaction between FIP200 and RIG-I triggers the innate immune response.