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Published on: July 16, 2012
Raf-1 kinase associates with Hepatitis C virus NS5A and regulates viral replication
T Bürckstümmer1, M Kriegs, J Lupberger
1Molecular Virology, Robert-Koch-Institut, Nordufer 20, 13353 Berlin, Germany. tbuerckstuemmer@cemm.oeaw.ac.at
Abstract:
Hepatitis C virus (HCV) is a positive-strand RNA virus that frequently causes persistent infection associated with severe liver disease. HCV nonstructural protein 5A (NS5A) is essential for viral replication. Here, the kinase Raf-1 was identified as a novel cellular binding partner of NS5A, binding to the C-terminal domain of NS5A. Raf-1 colocalizes with NS5A in the HCV replication complex. The interaction of NS5A with Raf-1 results in increased Raf-1 phosphorylation at serine 338. Integrity of Raf-1 is crucial for HCV replication: inhibition of Raf-1 by the small-molecule inhibitor BAY43-9006 or downregulation of Raf-1 by siRNA attenuates viral replication.
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