Redox Biology ( IF 11.4 ) Pub Date : 2021-10-18 , DOI: 10.1016/j.redox.2021.102172 Qianjin Liu 1 , Tianle Gu 1 , Ling-Yan Su 1 , Lijin Jiao 1 , Xinhua Qiao 2 , Min Xu 3 , Ting Xie 2 , Lu-Xiu Yang 3 , Dandan Yu 3 , Ling Xu 3 , Chang Chen 2 , Yong-Gang Yao 4
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.
中文翻译:
GSNOR通过限制TBK1半胱氨酸S-亚硝化促进抗病毒先天免疫
先天免疫是宿主抵御病原体的第一道防线。这一过程受到多种抗病毒蛋白修饰的调节,例如磷酸化和泛素化。在这里,我们发现细胞S-亚硝基谷胱甘肽还原酶 (GSNOR) 积极参与先天免疫激活。小鼠胚胎成纤维细胞 (MEFs) 和 RAW264.7 巨噬细胞中的 GSNOR 缺乏会降低抗病毒先天免疫反应并促进单纯疱疹病毒 1 (HSV-1) 和水疱性口炎病毒 (VSV) 的复制。一致地, Gsnor中的 HSV-1 感染-/-GSNOR 被 N6022 抑制的小鼠和野生型小鼠相对于各自的对照导致更高的死亡率,以及肺部免疫细胞的严重浸润。从机制上讲,GSNOR 缺乏增强了 Cys423 位点的细胞 TANK 结合激酶 1 (TBK1) 蛋白S-亚硝化并抑制了 TBK1 激酶活性,从而导致抗病毒反应的干扰素产生减少。我们的研究表明,GSNOR 是抗病毒反应的关键调节因子,S-亚硝化积极参与先天免疫。