Publication details

Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment.

Authors

REISS S. REBHAN Ilka BACKES P. ROMERO-BREY I. ERFLE Holger MATULA Petr KADERALI Lars POENISCH Marion BLANKENBURG H. HIET M.S. LONGERICH T. DIEHL S. RAMIREZ F. BALLA T. ROHR Karl KAUL A. BÜHLER S. PEPPERKOK Rainer LENGAUER T. ALBRECHT M. EILS Roland SCHIRMACHER P. LOHMANN V. BARTENSCHLAGER Ralf

Year of publication 2011
Type Article in Periodical
Magazine / Source Cell Host & Microbe
MU Faculty or unit

Faculty of Informatics

Citation
Doi http://dx.doi.org/10.1016/j.chom.2010.12.002
Field Microbiology, virology
Keywords RNA REPLICATION; PHOSPHATIDYLINOSITOL 4-KINASES; CELLULAR COFACTORS; CORE PROTEIN; HOST FACTORS; HUH-7 CELLS; INFECTION; COMPLEX; IDENTIFICATION; SCREEN
Description 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 (PI4KIIIalfa), as being required for HCV replication. Consistent with elevated levels of the PI4KIIIalfa product phosphatidylinositol-4-phosphate (PI4P) detected in HCV-infected cultured hepatocytes and liver tissue from chronic hepatitis C patients, the enzymatic activity of PI4KIIIalfa was critical for HCV replication. Viral nonstructural protein 5A (NS5A) was found to interact with PI4KIIIalfa and stimulate its kinase activity. The absence of PI4KIIIalfa 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.
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