tetano
Editor, Senior Moderator
Virus Res
. 2023 Mar 7;199086.
doi: 10.1016/j.virusres.2023.199086. Online ahead of print.
SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction
Ying Nie[SUP] 1 [/SUP], Lumin Mou[SUP] 2 [/SUP], Qizhou Long[SUP] 3 [/SUP], Dongqing Deng[SUP] 3 [/SUP], Rongying Hu[SUP] 4 [/SUP], Jinzhi Chen[SUP] 3 [/SUP], Jiahong Wu[SUP] 5 [/SUP]
Affiliations
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.
. 2023 Mar 7;199086.
doi: 10.1016/j.virusres.2023.199086. Online ahead of print.
SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction
Ying Nie[SUP] 1 [/SUP], Lumin Mou[SUP] 2 [/SUP], Qizhou Long[SUP] 3 [/SUP], Dongqing Deng[SUP] 3 [/SUP], Rongying Hu[SUP] 4 [/SUP], Jinzhi Chen[SUP] 3 [/SUP], Jiahong Wu[SUP] 5 [/SUP]
Affiliations
- 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.