Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment.
Cell Host Microbe
; 9(1): 32-45, 2011 Jan 20.
Article
en En
| MEDLINE
| ID: mdl-21238945
ABSTRACT
Hepatitis C virus (HCV) is a major causative agent of chronic liver disease in humans. To gain insight into host factor requirements for HCV replication, we performed a siRNA screen of the human kinome and identified 13 different kinases, including phosphatidylinositol-4 kinase III alpha (PI4KIIIα), as being required for HCV replication. Consistent with elevated levels of the PI4KIIIα product phosphatidylinositol-4-phosphate (PI4P) detected in HCV-infected cultured hepatocytes and liver tissue from chronic hepatitis C patients, the enzymatic activity of PI4KIIIα was critical for HCV replication. Viral nonstructural protein 5A (NS5A) was found to interact with PI4KIIIα and stimulate its kinase activity. The absence of PI4KIIIα activity induced a dramatic change in the ultrastructural morphology of the membranous HCV replication complex. Our analysis suggests that the direct activation of a lipid kinase by HCV NS5A contributes critically to the integrity of the membranous viral replication complex.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Replicación Viral
/
Proteínas no Estructurales Virales
/
Fosfotransferasas (Aceptor de Grupo Alcohol)
/
Hepacivirus
/
Interacciones Huésped-Patógeno
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Host Microbe
Asunto de la revista:
MICROBIOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania