tetano
Editor, Senior Moderator
iScience
. 2023 Aug 23;26(9):107705.
doi: 10.1016/j.isci.2023.107705. eCollection 2023 Sep 15. SARS-CoV-2 Nsp15 suppresses type I interferon production by inhibiting IRF3 phosphorylation and nuclear translocation
Dianqi Zhang[SUP] 1 2 3 [/SUP], Likai Ji[SUP] 2 [/SUP], Xu Chen[SUP] 2 4 [/SUP], Yumin He[SUP] 2 5 [/SUP], Yijie Sun[SUP] 2 [/SUP], Li Ji[SUP] 2 [/SUP], Tiancheng Zhang[SUP] 2 [/SUP], Quan Shen[SUP] 2 [/SUP], Xiaochun Wang[SUP] 2 [/SUP], Yan Wang[SUP] 2 [/SUP], Shixing Yang[SUP] 1 2 [/SUP], Wen Zhang[SUP] 1 2 [/SUP], Chenglin Zhou[SUP] 1 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), poses a significant threat to global public health security. Like other coronaviruses, SARS-CoV-2 has developed various strategies to inhibit the production of interferon (IFN). Here, we have discovered that SARS-CoV-2 Nsp15 obviously reduces the expression of IFN-β and IFN-stimulated genes (ISG56, CXCL10), and also inhibits IRF3 phosphorylation and nuclear translocation by antagonizing the RLR-mediated antiviral signaling pathway. Mechanically, we found that the poly-U-specific endonuclease domain (EndoU) of Nsp15 directly associates with the kinase domain (KD) of TBK1 to interfere TBK1 interacting with IRF3 and the flowing TBK1-mediated IRF3 phosphorylation. Furthermore, Nsp15 also prevented nuclear translocation of phosphorylated IRF3 via binding to the nuclear import adaptor karyopherin α1 (KPNA1) and promoting it autophagy-dependent degradation. These findings collectively reveal a novel mechanism by which Nsp15 antagonizes host's innate immune response.
Keywords: Cell biology; Immunology; Virology.
. 2023 Aug 23;26(9):107705.
doi: 10.1016/j.isci.2023.107705. eCollection 2023 Sep 15. SARS-CoV-2 Nsp15 suppresses type I interferon production by inhibiting IRF3 phosphorylation and nuclear translocation
Dianqi Zhang[SUP] 1 2 3 [/SUP], Likai Ji[SUP] 2 [/SUP], Xu Chen[SUP] 2 4 [/SUP], Yumin He[SUP] 2 5 [/SUP], Yijie Sun[SUP] 2 [/SUP], Li Ji[SUP] 2 [/SUP], Tiancheng Zhang[SUP] 2 [/SUP], Quan Shen[SUP] 2 [/SUP], Xiaochun Wang[SUP] 2 [/SUP], Yan Wang[SUP] 2 [/SUP], Shixing Yang[SUP] 1 2 [/SUP], Wen Zhang[SUP] 1 2 [/SUP], Chenglin Zhou[SUP] 1 [/SUP]
Affiliations
- PMID: 37680466
- PMCID: PMC10480782
- DOI: 10.1016/j.isci.2023.107705
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), poses a significant threat to global public health security. Like other coronaviruses, SARS-CoV-2 has developed various strategies to inhibit the production of interferon (IFN). Here, we have discovered that SARS-CoV-2 Nsp15 obviously reduces the expression of IFN-β and IFN-stimulated genes (ISG56, CXCL10), and also inhibits IRF3 phosphorylation and nuclear translocation by antagonizing the RLR-mediated antiviral signaling pathway. Mechanically, we found that the poly-U-specific endonuclease domain (EndoU) of Nsp15 directly associates with the kinase domain (KD) of TBK1 to interfere TBK1 interacting with IRF3 and the flowing TBK1-mediated IRF3 phosphorylation. Furthermore, Nsp15 also prevented nuclear translocation of phosphorylated IRF3 via binding to the nuclear import adaptor karyopherin α1 (KPNA1) and promoting it autophagy-dependent degradation. These findings collectively reveal a novel mechanism by which Nsp15 antagonizes host's innate immune response.
Keywords: Cell biology; Immunology; Virology.