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

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

  • Mol Immunol. 2024 Sep 11:175:1-9. doi: 10.1016/j.molimm.2024.09.001.
Weiling Li 1,  Yuansong Wang 1,  Qian Peng 1,  Yingying Shi 2,  Pin Wan 1,  Yulin Yao 1,  Tao Bai 3,  Yanling Ma 4,  Xiji Shu 1,  Yuchen Liu 5,  Binlian Sun 6
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Cognitive and Affective Disorders, Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, China.
  • 2 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.
  • 3 Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 4 Division of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 5 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.
  • 6 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.
PMID: 39265360 DOI: 10.1016/j.molimm.2024.09.001
Abstract

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.

Keywords

AP-1; Inflammation; NSP14; RAF/MEK/ERK; SARS-CoV-2.

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