Huang, C.; Yin, Y.; Pan, P.; Huang, Y.; Chen, S.; Chen, J.; Wang, J.; Xu, G.; Tao, X.; Xiao, X.; Li, J.; Yang, J.; Jin, Z.; Li, B.; Tong, Z.; Du, W.; Liu, L.; Liu, Z. The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation. Viruses2023, 15, 2304.
Huang, C.; Yin, Y.; Pan, P.; Huang, Y.; Chen, S.; Chen, J.; Wang, J.; Xu, G.; Tao, X.; Xiao, X.; Li, J.; Yang, J.; Jin, Z.; Li, B.; Tong, Z.; Du, W.; Liu, L.; Liu, Z. The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation. Viruses 2023, 15, 2304.
Huang, C.; Yin, Y.; Pan, P.; Huang, Y.; Chen, S.; Chen, J.; Wang, J.; Xu, G.; Tao, X.; Xiao, X.; Li, J.; Yang, J.; Jin, Z.; Li, B.; Tong, Z.; Du, W.; Liu, L.; Liu, Z. The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation. Viruses2023, 15, 2304.
Huang, C.; Yin, Y.; Pan, P.; Huang, Y.; Chen, S.; Chen, J.; Wang, J.; Xu, G.; Tao, X.; Xiao, X.; Li, J.; Yang, J.; Jin, Z.; Li, B.; Tong, Z.; Du, W.; Liu, L.; Liu, Z. The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation. Viruses 2023, 15, 2304.
Abstract
Severe COVID-19 patients show impaired IFN-I response due to decreased IFN-β production, allowing persistent viral load and exacerbated inflammation. The SARS-CoV-2 nucleocapsid protein has been implicated in inhibiting IFN-I response through interfering with IFN-I signaling. This study reveals that SARS-CoV-2 nucleocapsid protein enhances interaction between human SUMO-conjugating enzyme UBC9 and MAVS. Increased MAVS-UBC9 interaction leads to enhanced SUMOylation of MAVS, inhibiting its ubiquitination, resulting in the inhibition of phosphorylation events involving IKKα, TBK1, and IRF3, disrupting IFN-I signaling. These results provide essential insights into the intricate regulation of the host's innate immunity during SARS-COV-2 invasion. Understanding these complex molecular mechanisms is crucial in developing effective therapeutic interventions against COVID-19 and potential future viral outbreaks.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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