The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation

Autor: Congcong Huang, Yiping Yin, Pan Pan, Yanping Huang, Siwei Chen, Junkai Chen, Ju Wang, Guoqing Xu, Xuan Tao, Xiao Xiao, Jian Li, Jing Yang, Zhixiong Jin, Bei Li, Zhaohui Tong, Weixing Du, Long Liu, Zhixin Liu
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Viruses, Vol 15, Iss 12, p 2304 (2023)
Druh dokumentu: article
ISSN: 1999-4915
DOI: 10.3390/v15122304
Popis: Severe COVID-19 patients exhibit impaired IFN-I response due to decreased IFN-β production, allowing persistent viral load and exacerbated inflammation. While the SARS-CoV-2 nucleocapsid (N) protein has been implicated in inhibiting innate immunity by interfering with IFN-β signaling, the specific underlying mechanism still needs further investigation for a comprehensive understanding. This study reveals that the SARS-CoV-2 N protein enhances interaction between the 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, thus disrupting IFN-β signaling. This study highlights the role of the N protein of SARS-CoV-2 in modulating the innate immune response by affecting the MAVS SUMOylation and ubiquitination processes, leading to inhibition of the IFN-β signaling pathway. These findings shed light on the complex mechanisms utilized by SARS-CoV-2 to manipulate the host’s antiviral defenses and provide potential insights for developing targeted therapeutic strategies against severe COVID-19.
Databáze: Directory of Open Access Journals