Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3.
Virology
; 515: 165-175, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29294448
ABSTRACT
Severe acute respiratory syndrome coronavirus (SARS-CoV) is an inefficient inducer of interferon (IFN) response. It expresses various proteins that effectively circumvent IFN production at different levels via distinct mechanisms. Through the construction of recombinant IBV expressing proteins 8a, 8b and 8ab encoded by SARS-CoV ORF8, we demonstrate that expression of 8b and 8ab enables the corresponding recombinant viruses to partially overcome the inhibitory actions of IFN activation to achieve higher replication efficiencies in cells. We also found that proteins 8b and 8ab could physically interact with IRF3. Overexpression of 8b and 8ab resulted in the reduction of poly (IC)-induced IRF3 dimerization and inhibition of the IFN-ß signaling pathway. This counteracting effect was partially mediated by protein 8b/8ab-induced degradation of IRF3 in a ubiquitin-proteasome-dependent manner. Taken together, we propose that SARS-CoV may exploit the unique functions of proteins 8b and 8ab as novel mechanisms to overcome the effect of IFN response during virus infection.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ubiquitina
/
Síndrome Respiratória Aguda Grave
/
Coronavírus Relacionado à Síndrome Respiratória Aguda Grave
/
Fator Regulador 3 de Interferon
/
Proteínas Virais Reguladoras e Acessórias
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article