Hepatitis C virus exploits cyclophilin A to evade PKR.
Elife
; 92020 06 16.
Article
en En
| MEDLINE
| ID: mdl-32539931
ABSTRACT
Counteracting innate immunity is essential for successful viral replication. Host cyclophilins (Cyps) have been implicated in viral evasion of host antiviral responses, although the mechanisms are still unclear. Here, we show that hepatitis C virus (HCV) co-opts the host protein CypA to aid evasion of antiviral responses dependent on the effector protein kinase R (PKR). Pharmacological inhibition of CypA rescues PKR from antagonism by HCV NS5A, leading to activation of an interferon regulatory factor-1 (IRF1)-driven cell intrinsic antiviral program that inhibits viral replication. These findings further the understanding of the complexity of Cyp-virus interactions, provide mechanistic insight into the remarkably broad antiviral spectrum of Cyp inhibitors, and uncover novel aspects of PKR activity and regulation. Collectively, our study identifies a novel antiviral mechanism that harnesses cellular antiviral immunity to suppress viral replication.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Replicación Viral
/
Proteínas no Estructurales Virales
/
Hepacivirus
/
EIF-2 Quinasa
/
Ciclofilina A
/
Factor 1 Regulador del Interferón
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Elife
Año:
2020
Tipo del documento:
Article
País de afiliación:
Canadá