2. Academic Validation
  3. SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction

SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction

  • Virus Res. 2023 Apr 15;328:199086. doi: 10.1016/j.virusres.2023.199086.
Ying Nie 1,  Lumin Mou 2,  Qizhou Long 3,  Dongqing Deng 3,  Rongying Hu 4,  Jinzhi Cheng 3,  Jiahong Wu 5
Affiliations

Affiliations

  • 1 Department of Parasitology, Provincial Key Laboratory of Modern Pathogen Biology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, China; These authors contributed equally: Ying Nie, Lumin Mou.
  • 2 Department of Parasitology, Provincial Key Laboratory of Modern Pathogen Biology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, China; Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 550025, China; These authors contributed equally: Ying Nie, Lumin Mou.
  • 3 Department of Parasitology, Provincial Key Laboratory of Modern Pathogen Biology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, China.
  • 4 The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.
  • 5 Department of Parasitology, Provincial Key Laboratory of Modern Pathogen Biology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, China; Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 550025, China. Electronic address: jiahongw@gmc.edu.cn.
PMID: 36894068 DOI: 10.1016/j.virusres.2023.199086
Abstract

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 Infection. Patients with severe COVID-19 exhibit robust induction of proinflammatory cytokines, which are closely associated with the development of acute respiratory distress syndrome. However, the underlying mechanisms of the NF-κB activation mediated by SARS-CoV-2 Infection remain poorly understood. Here, we screened SARS-CoV-2 genes and found that ORF3a induces proinflammatory cytokines by activating the NF-κB pathway. Moreover, we found that ORF3a interacts with IKKβ and NEMO and enhances the interaction of IKKβ-NEMO, thereby positively regulating NF-κB activity. Together, these results suggest ORF3a may play pivotal roles in the pathogenesis of SARS-CoV-2 and provide novel insights into the interaction between host immune responses and SARS-CoV-2 Infection.

Keywords

IKKβ; Inflammation; NEMO; NF-κB; ORF3a; SARS-CoV-2.

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