DDX56 antagonizes IFN-ß production to enhance EMCV replication by inhibiting IRF3 nuclear translocation.
Vet Microbiol
; 264: 109304, 2022 Jan.
Article
em En
| MEDLINE
| ID: mdl-34922148
ABSTRACT
DEAD (Asp-Glu-Ala-Asp)-box RNA helicases (DDX) play important roles in viral infection, either as cytosolic viral nucleic acids sensors or as essential host factors for viral replication. In this study, we identified DDX56 as a positive regulator for encephalomyocarditis virus (EMCV) replication. EMCV infection promotes DDX56 expression via its viral proteins, VP3 and 3C. We showed that DDX56 overexpression promotes EMCV replication whereas its loss dampened EMCV replication. Consequently, knockdown of DDX56 increases type I interferon (IFN) expression during EMCV infection. We also showed that DDX56 interrupts IFN regulatory factor 3 (IRF3) phosphorylation and its nucleus translocation by directly targeting KPNA3 and KPNA4 in an EMCV-triggered MDA5 signaling activation cascade leading to the blockade of IFN-ß production. Overall, we showed that DDX56 is a novel negative regulator of EMCV-mediated IFN-ß responses and that DDX56 plays a critical role in EMCV replication. These findings reveal a novel strategy for EMCV to utilize a host factor to evade the host innate immune response and provide us new insight into the function of DDX56.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
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Interferon beta
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Transporte Proteico
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Vírus da Encefalomiocardite
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Fator Regulador 3 de Interferon
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RNA Helicases DEAD-box
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Interações Hospedeiro-Patógeno
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Vet Microbiol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China