Redox Biology, 18 October, 2021, DOI：https://doi.org/10.1016/j.redox.2021.102172
GSNOR facilitates antiviral innate immunity by restricting TBK1 cysteine S-nitrosation
Qianjin Liu, Tianle Gu, Ling-Yan Su, Lijin Jiao, Xinhua Qiao, Min Xu, Ting Xie, Lu-Xiu Yang, Dandan Yu, Ling Xu, Chang Chen, Yong-Gang Yao
Innate immunity is the first line of host defense against pathogens. This process is modulated by multiple antiviral protein modifications, such as phosphorylation and ubiquitination. Here, we showed that cellular S-nitrosoglutathione reductase (GSNOR) is actively involved in innate immunity activation. GSNOR deficiency in mouse embryo fibroblasts (MEFs) and RAW264.7 macrophages reduced the antiviral innate immune response and facilitated herpes simplex virus-1 (HSV-1) and vesicular stomatitis virus (VSV) replication. Concordantly, HSV-1 infection in Gsnor-/- mice and wild-type mice with GSNOR being inhibited by N6022 resulted in higher mortality relative to the respective controls, together with severe infiltration of immune cells in the lungs. Mechanistically, GSNOR deficiency enhanced cellular TANK-binding kinase 1 (TBK1) protein S-nitrosation at the Cys423 site and inhibited TBK1 kinase activity, resulting in reduced interferon production for antiviral responses. Our study indicated that GSNOR is a critical regulator of antiviral responses and S-nitrosation is actively involved in innate immunity.