tetano
Editor, Senior Moderator
J Cell Biol
. 2025 Jan 6;224(1):e202404131.
doi: 10.1083/jcb.202404131. Epub 2024 Dec 16. SARS-CoV-2 specific adaptations in N protein inhibit NF-κB activation and alter pathogenesis
Xiao Guo[SUP] #[/SUP][SUP] 1 [/SUP], Shimin Yang[SUP] #[/SUP][SUP] 1 [/SUP], Zeng Cai[SUP] #[/SUP][SUP] 2 [/SUP], Shunhua Zhu[SUP] 1 [/SUP], Hongyun Wang[SUP] 1 [/SUP], Qianyun Liu[SUP] 1 [/SUP], Zhen Zhang[SUP] 1 [/SUP], Jiangpeng Feng[SUP] 1 [/SUP], Xianying Chen[SUP] 1 [/SUP], Yingjian Li[SUP] 1 [/SUP], Jikai Deng[SUP] 1 [/SUP], Jiejie Liu[SUP] 1 [/SUP], Jiali Li[SUP] 1 [/SUP], Xue Tan[SUP] 1 [/SUP], Zhiying Fu[SUP] 1 [/SUP], Ke Xu[SUP] 1 [/SUP], Li Zhou[SUP] 2 [/SUP], Yu Chen[SUP] 1 2 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV) exhibit differences in their inflammatory responses and pulmonary damage, yet the specific mechanisms remain unclear. Here, we discovered that the SARS-CoV-2 nucleocapsid (N) protein inhibits the activation of the nuclear factor-κB (NF-κB) pathway and downstream signal transduction by impeding the assembly of the transforming growth factor β-activated kinase1 (TAK1)-TAK1 binding protein 2/3 (TAB2/3) complex. In contrast, the SARS-CoV N protein does not impact the NF-κB pathway. By comparing the amino acid sequences of the SARS-CoV-2 and SARS-CoV N proteins, we identified Glu-290 and Gln-349 as critical residues in the C-terminal domain (CTD) of the SARS-CoV-2 N protein, essential for its antagonistic function. These findings were further validated in a SARS-CoV-2 trans-complementation system using cellular and animal models. Our results reveal the distinctions in inflammatory responses triggered by SARS-CoV-2 and SARS-CoV, highlighting the significance of specific amino acid alterations in influencing viral pathogenicity.
. 2025 Jan 6;224(1):e202404131.
doi: 10.1083/jcb.202404131. Epub 2024 Dec 16. SARS-CoV-2 specific adaptations in N protein inhibit NF-κB activation and alter pathogenesis
Xiao Guo[SUP] #[/SUP][SUP] 1 [/SUP], Shimin Yang[SUP] #[/SUP][SUP] 1 [/SUP], Zeng Cai[SUP] #[/SUP][SUP] 2 [/SUP], Shunhua Zhu[SUP] 1 [/SUP], Hongyun Wang[SUP] 1 [/SUP], Qianyun Liu[SUP] 1 [/SUP], Zhen Zhang[SUP] 1 [/SUP], Jiangpeng Feng[SUP] 1 [/SUP], Xianying Chen[SUP] 1 [/SUP], Yingjian Li[SUP] 1 [/SUP], Jikai Deng[SUP] 1 [/SUP], Jiejie Liu[SUP] 1 [/SUP], Jiali Li[SUP] 1 [/SUP], Xue Tan[SUP] 1 [/SUP], Zhiying Fu[SUP] 1 [/SUP], Ke Xu[SUP] 1 [/SUP], Li Zhou[SUP] 2 [/SUP], Yu Chen[SUP] 1 2 [/SUP]
Affiliations
- PMID: 39680116
- DOI: 10.1083/jcb.202404131
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV) exhibit differences in their inflammatory responses and pulmonary damage, yet the specific mechanisms remain unclear. Here, we discovered that the SARS-CoV-2 nucleocapsid (N) protein inhibits the activation of the nuclear factor-κB (NF-κB) pathway and downstream signal transduction by impeding the assembly of the transforming growth factor β-activated kinase1 (TAK1)-TAK1 binding protein 2/3 (TAB2/3) complex. In contrast, the SARS-CoV N protein does not impact the NF-κB pathway. By comparing the amino acid sequences of the SARS-CoV-2 and SARS-CoV N proteins, we identified Glu-290 and Gln-349 as critical residues in the C-terminal domain (CTD) of the SARS-CoV-2 N protein, essential for its antagonistic function. These findings were further validated in a SARS-CoV-2 trans-complementation system using cellular and animal models. Our results reveal the distinctions in inflammatory responses triggered by SARS-CoV-2 and SARS-CoV, highlighting the significance of specific amino acid alterations in influencing viral pathogenicity.