PACT is required for MDA5-mediated immunoresponses triggered by Cardiovirus infection via interaction with LGP2.
Biochem Biophys Res Commun
; 494(1-2): 227-233, 2017 12 09.
Article
en En
| MEDLINE
| ID: mdl-29032202
ABSTRACT
Laboratory of genetics and physiology 2 (LGP2) and melanoma differentiation-associated gene 5 (MDA5) cooperatively detect viral RNA in the cytoplasm of Cardiovirus-infected cells and activate innate immune responses. Here, we evaluated whether the double-stranded RNA-binding protein PACT plays a role in this anti-viral response to further elucidate the mechanism. Immunoprecipitation experiments demonstrated that PACT interacts with LGP2 and that this interaction is enhanced by encephalomyocarditis virus (EMCV) infection. In vitro interaction analyses using purified recombinant proteins confirmed that the single-stranded Theiler's murine encephalitis virus genome enhanced the interaction between LGP2 and PACT. Small interfering RNA knockdown experiments further indicated that PACT is required for Cardiovirus-triggered interferon responses. To support this functional interaction with LGP2, overexpressed PACT was shown to enhance EMCV-triggered interferon promoter activity only when LGP2 and MDA5 were co-expressed but not when MDA5 is expressed alone. Together, our findings indicate a possible role of PACT in regulating the Cardiovirus-triggered immune responses mediated by MDA5 and LGP2, which opens the door to novel therapeutic strategies in interferon-related autoimmune diseases and cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Unión al ARN
/
Infecciones por Cardiovirus
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ARN Helicasas
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Virus de la Encefalomiocarditis
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Helicasa Inducida por Interferón IFIH1
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón