LncRNA-GM Facilitates Antiviral Innate Immunity by Binding GSTM1 to Reduce S-glutathionylation and Enhance Activity of TBK1
62 Pages Posted: 28 Oct 2019 Sneak Peek Status: Review CompleteMore...
Viruses evolve multiple strategies to evade host immune elimination. How host lncRNAs are utilized by viruses for immune evasion remains further investigation. By screening virus infection-downregulated lncRNAs in macrophages, we identified a S-glutathionylation modification-related lncRNA (lncRNA-GM) which promotes antiviral type I interferon (IFN-I) production by enhancing TBK1 kinase activity. Mechanistically, lncRNA-GM bound glutathione S-transferase M1 (GSTM1) and blocked its interaction with TBK1, thus preventing GSTM1-mediated S-glutathionylation of TBK1 and enhancing TBK1 activity. Accordingly, viral infection-reprogrammed intracellular glutathione metabolism inhibited TBK1 activity and IFN-I induction. lncRNA-GM-deficient mice exhibited more susceptibility to virus challenge, accompanied by impaired IFN-I production. Therefore, viral infection down-regulates lncRNA-GM, resulting in the increased S-glutathionylation of TBK1 with reduced kinase activity and eventually impairing innate immunity for helping viral evasion. Our results provide mechanistic insight into lncRNA modulation of antiviral innate response and identify the new roles of metabolite glutathione and TBK1 S-glutathionylation in antiviral immune network.
Keywords: lncRNA, TBK1, S-glutathionylation, Glutathione S-transferase, Antiviral innate immunity
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