Induction of Siglec-G by RNA viruses inhibits the innate immune response by promoting RIG-I degradation.
Cell
; 152(3): 467-78, 2013 Jan 31.
Article
en En
| MEDLINE
| ID: mdl-23374343
ABSTRACT
RIG-I is a critical RNA virus sensor that serves to initiate antiviral innate immunity. However, posttranslational regulation of RIG-I signaling remains to be fully understood. We report here that RNA viruses, but not DNA viruses or bacteria, specifically upregulate lectin family member Siglecg expression in macrophages by RIG-I- or NF-κB-dependent mechanisms. Siglec-G-induced recruitment of SHP2 and the E3 ubiquitin ligase c-Cbl to RIG-I leads to RIG-I degradation via K48-linked ubiquitination at Lys813 by c-Cbl. By increasing type I interferon production, targeted inactivation of Siglecg protects mice against lethal RNA virus infection. Taken together, our data reveal a negative feedback loop of RIG-I signaling and identify a Siglec-G-mediated immune evasion pathway exploited by RNA viruses with implication in antiviral applications. These findings also provide insights into the functions and crosstalk of Siglec-G, a known adaptive response regulator, in innate immunity.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Infecciones por Virus ARN
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Receptores de Antígenos de Linfocitos B
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Infecciones por Bacterias Gramnegativas
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ARN Helicasas DEAD-box
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Inmunidad Innata
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Lectinas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2013
Tipo del documento:
Article