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

作者：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 · 发表于：Preprints.org · 年份：2023 · DOI：10.20944/preprints202310.1507.v1 · 被引用次数：1 · 研究领域：interferon and immune responses、Ubiquitin and proteasome pathways、Inflammasome and immune disorders

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.