Raf-1 kinase associates with Hepatitis C virus NS5A and regulates viral replication

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...

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Bibliographic Details
Published in:FEBS letters 2006-01, Vol.580 (2), p.575-580
Main Authors: Bürckstümmer, T., Kriegs, M., Lupberger, J., Pauli, E.K., Schmittel, S., Hildt, E.
Format: Article
Language:English
Subjects:
Animals
Benzenesulfonates - metabolism
HCV
Hepacivirus - genetics
Hepacivirus - metabolism
Hepatitis C virus
Molecular Sequence Data
Niacinamide - analogs & derivatives
NS5A
Phenylurea Compounds
Protein Binding
Proto-Oncogene Proteins c-raf - genetics
Proto-Oncogene Proteins c-raf - metabolism
Pyridines - metabolism
Raf-1
Replication
Replicon
RNA, Small Interfering - metabolism
RNA-Dependent RNA Polymerase - metabolism
Sorafenib
Viral Nonstructural Proteins - metabolism
Virus Replication - physiology
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Summary: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.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2005.12.071