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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzenesulfonates / metabolism
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Hepacivirus / genetics
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Hepacivirus / metabolism*
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Molecular Sequence Data
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Niacinamide / analogs & derivatives
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Phenylurea Compounds
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Protein Binding
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Proto-Oncogene Proteins c-raf / genetics
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Proto-Oncogene Proteins c-raf / metabolism*
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Pyridines / metabolism
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RNA, Small Interfering / metabolism
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RNA-Dependent RNA Polymerase / metabolism
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Replicon
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Sorafenib
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Viral Nonstructural Proteins / metabolism*
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Virus Replication / physiology*
Substances
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Benzenesulfonates
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Phenylurea Compounds
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Pyridines
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RNA, Small Interfering
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Viral Nonstructural Proteins
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Niacinamide
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Sorafenib
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Proto-Oncogene Proteins c-raf
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NS-5 protein, hepatitis C virus
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RNA-Dependent RNA Polymerase