E3 ligase FBXW7 is critical for RIG-I stabilization during antiviral responses

• Published in: Nature communications Vol. 8; no. 1; pp. 14654 - 14
• Main Authors: Song, Yinjing, Lai, Lihua, Chong, Zhenlu, He, Jia, Zhang, Yuanyuan, Xue, Yue, Xie, Yiwei, Chen, Songchang, Dong, Ping, Chen, Luoquan, Chen, Zhimin, Dai, Feng, Wan, Xiaopeng, Xiao, Peng, Cao, Xuetao, Liu, Yang, Wang, Qingqing
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.03.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/109; 13/89; 14; 14/19; 38; 38/77; 631/250/256; 631/250/262; 631/326/596/2557; 64; 64/60; 692/699/255/2514; 82; 82/29; 96; 96/34; Cytoplasm; Humanities and Social Sciences; Immunology; Infections; Medicine; multidisciplinary; Neurosciences; Proteins; Respiratory syncytial virus; Science; Science (multidisciplinary); Transcription factors; Viral infections; Viruses; China
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14654

Viruses can escape from host recognition by degradation of RIG-I or interference with the RIG-I signalling to establish persistent infections. However, the mechanisms by which host cells stabilize RIG-I protein for avoiding its degradation are largely unknown. We report here that, upon virus infection, the E3 ubiquitin ligase FBXW7 translocates from the nucleus into the cytoplasm and stabilizes RIG-I. FBXW7 interacts with SHP2 and mediates the degradation and ubiquitination of SHP2, thus disrupting the SHP2/c-Cbl complex, which mediates RIG-I degradation. When infected with VSV or influenza A virus, FBXW7 conditional knockout mice (Lysm + FBXW7 f/f ) show impaired antiviral immunity. FBXW7-deficient macrophages have decreased RIG-I protein levels and type-I interferon signalling. Furthermore, PBMCs from RSV-infected children have reduced FBXW7 mRNA levels. Our results identify FBXW7 as an important interacting partner for RIG-I. These findings provide insights into the function of FBXW7 in antiviral immunity and its related clinical significance. The innate immune response to many RNA viruses depends on recognition of viral RNA by RIG-I. Here the authors show that, upon virus infection, FBXW7 interacts with RIG-I and inhibits ubiquitin-mediated degradation of RIG-I, resulting in increased interferon signalling in vitro and in vivo .