HCV NS5A co-operates with PKR in modulating HCV IRES-dependent translation.
Infect Genet Evol
; 26: 113-22, 2014 Aug.
Article
en En
| MEDLINE
| ID: mdl-24815730
ABSTRACT
Translation initiation of the Hepatitis C virus (HCV) genome is driven by an internal ribosome entry site (IRES), located within the 5' non-coding region. Several studies have suggested that different cellular non canonical proteins or viral proteins can regulate the HCV IRES activity. However, the role of the viral proteins on HCV translation remains controversial. In this report, we confirmed previous studies showing that NS5A down-regulates IRES activity in HepG2 but not in Huh7 cells suggesting that the NS5A effect on HCV IRES is cell-type dependent. Additionally, we provide strong evidence that activated PKR up-regulates the IRES activity while silencing of endogenous PKR had the opposite effect. Furthermore, we present data indicating that the NS5A-mediated inhibitory effect on IRES-dependent translation could be linked with the PKR inactivation. Finally, we show that NS5A from GBV-C but not from GBV-B down-regulates HCV IRES activity in the absence or the presence of PKR over expression. Notably, HCV and GBV-C but not GBV-B NS5A contains a previously identified PKR interacting protein domain.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Biosíntesis de Proteínas
/
Proteínas no Estructurales Virales
/
Hepacivirus
/
EIF-2 Quinasa
/
Regiones no Traducidas 5'
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Infect Genet Evol
Asunto de la revista:
BIOLOGIA
/
DOENCAS TRANSMISSIVEIS
/
GENETICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Grecia