The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation.
Viruses
; 15(12)2023 11 24.
Article
de En
| MEDLINE
| ID: mdl-38140545
ABSTRACT
Severe COVID-19 patients exhibit impaired IFN-I response due to decreased IFN-ß 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-ß 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-ß 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-ß 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
SARS-CoV-2
/
COVID-19
Limites:
Humans
Langue:
En
Journal:
Viruses
Année:
2023
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Suisse