SARS-CoV-2 NSP14 induces AP-1 transcriptional activity via its interaction with MEK.

Autor: Li W; Hubei Key Laboratory of Cognitive and Affective Disorders, Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China., Wang Y; Hubei Key Laboratory of Cognitive and Affective Disorders, Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China., Peng Q; Hubei Key Laboratory of Cognitive and Affective Disorders, Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China., Shi Y; Hubei Key Laboratory of Cognitive and Affective Disorders, Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China; Department of Immunology, School of Medicine, Jianghan University, Wuhan, China., Wan P; Hubei Key Laboratory of Cognitive and Affective Disorders, Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China., Yao Y; Hubei Key Laboratory of Cognitive and Affective Disorders, Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China., Bai T; Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Ma Y; Division of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Shu X; Hubei Key Laboratory of Cognitive and Affective Disorders, Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China., Liu Y; Hubei Key Laboratory of Cognitive and Affective Disorders, Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China. Electronic address: yuchen.liu@jhun.edu.cn., Sun B; Hubei Key Laboratory of Cognitive and Affective Disorders, Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China; Department of Immunology, School of Medicine, Jianghan University, Wuhan, China. Electronic address: binlian17@jhun.edu.cn.
Jazyk: angličtina
Zdroj: Molecular immunology [Mol Immunol] 2024 Nov; Vol. 175, pp. 1-9. Date of Electronic Publication: 2024 Sep 11.
DOI: 10.1016/j.molimm.2024.09.001
Abstrakt: The NSP14 protein of SARS-CoV-2 not only facilitates viral replication but also plays a pivotal role in activating the host immune system by enhancing cytokine production. In this study, we found that NSP14 markedly activated the activator protein 1 (AP-1) pathway by increasing the phosphorylation of ERK (p-ERK), which enters the nucleus and promotes AP-1 transcription. The screening of the main proteins of the ERK pathway revealed that NSP14 could interact with MEK, a kinase of ERK, and increase the level of phosphorylated MEK. The addition of the MEK inhibitor U0126 suppressed the level of p-ERK induced by NSP14 and partly blocked cytokine production, suggesting that NSP14 activates MEK to enhance AP-1 signaling. Further investigation demonstrated that the ExoN domain of NSP14 might be crucial for the interaction and activation of MEK. These results suggest a novel mechanism by which NSP14 of SARS-CoV-2 induces a proinflammatory response in the host.
Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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