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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 Complete

See all articles by Yujia Wang

Yujia Wang

Zhejiang University - Institute of Immunology

Junfang Xu

Second Military Medical University - National Key Laboratory of Medical Immunology

Pin Wang

Second Military Medical University - National Key Laboratory of Medical Immunology

Yunkai Zhang

Second Military Medical University - National Key Laboratory of Medical Immunology

Zhiqing Li

Second Military Medical University - National Key Laboratory of Medical Immunology

Zemeng Li

Second Military Medical University - National Key Laboratory of Medical Immunology

Zhongcheng Zhou

Nankai University - State Key Laboratory of Medicinal Chemical Biology

Lin Liu

Nankai University - State Key Laboratory of Medicinal Chemical Biology

Xuetao Cao

Second Military Medical University - National Key Laboratory of Medical Immunology

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Abstract

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

Suggested Citation

Wang, Yujia and Xu, Junfang and Wang, Pin and Zhang, Yunkai and Li, Zhiqing and Li, Zemeng and Zhou, Zhongcheng and Liu, Lin and Cao, Xuetao, LncRNA-GM Facilitates Antiviral Innate Immunity by Binding GSTM1 to Reduce S-glutathionylation and Enhance Activity of TBK1 (October 25, 2019). Available at SSRN: https://ssrn.com/abstract=3475206 or http://dx.doi.org/10.2139/ssrn.3475206
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Yujia Wang

Zhejiang University - Institute of Immunology

Hangzhou, 310058
China

Junfang Xu

Second Military Medical University - National Key Laboratory of Medical Immunology

Shanghai, 200433
China

Pin Wang

Second Military Medical University - National Key Laboratory of Medical Immunology

Shanghai, 200433
China

Yunkai Zhang

Second Military Medical University - National Key Laboratory of Medical Immunology

Shanghai, 200433
China

Zhiqing Li

Second Military Medical University - National Key Laboratory of Medical Immunology

Shanghai, 200433
China

Zemeng Li

Second Military Medical University - National Key Laboratory of Medical Immunology

Shanghai, 200433
China

Zhongcheng Zhou

Nankai University - State Key Laboratory of Medicinal Chemical Biology

Haihe Education Park
38 Tongyan Road
Tianjin, 300353
China

Lin Liu

Nankai University - State Key Laboratory of Medicinal Chemical Biology

Haihe Education Park
38 Tongyan Road
Tianjin, 300353
China

Xuetao Cao (Contact Author)

Second Military Medical University - National Key Laboratory of Medical Immunology ( email )

Shanghai, 200433
China

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