Citation
- Authors: Song, Y., Lai, L., Chong, Z., He, J., Zhang, Y., Xue, Y., Xie, Y., Chen, S., Dong, P., Chen, L., Chen, Z., Dai, F., Wan, X., Xiao, P., Cao, X., Liu, Y., Wang, Q.
- Year: 2017
- Journal: Nat Commun 8 14654
- Applications: in vitro / DNA, siRNA / INTERFERin, jetPRIME
- Cell types:
- Name: Dendritic cells
- Name: HEK-293T
Description: Human embryonic kidney Fibroblast
Known as: HEK293T, 293T - Name: Human macrophages
Description: Human macrophages
Abstract
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.