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.
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.
Virus Res. 2023 Apr 15;328:199086. doi: 10.1016/j.virusres.2023.199086. Epub 2023 Mar 13.
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.
新型冠状病毒病（COVID-19）是由 SARS-CoV-2 感染引起的全球大流行疾病。重症 COVID-19 患者表现出强烈的促炎细胞因子诱导，这与急性呼吸窘迫综合征的发生密切相关。然而，SARS-CoV-2 感染介导的 NF-κB 激活的潜在机制仍知之甚少。在这里，我们筛选了 SARS-CoV-2 基因，发现 ORF3a 通过激活 NF-κB 通路诱导促炎细胞因子。此外，我们发现 ORF3a 与 IKKβ 和 NEMO 相互作用，并增强 IKKβ-NEMO 的相互作用，从而正向调节 NF-κB 活性。总之，这些结果表明 ORF3a 可能在 SARS-CoV-2 的发病机制中发挥关键作用，并为宿主免疫反应与 SARS-CoV-2 感染之间的相互作用提供了新的见解。
