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 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.
Bürckstümmer
T
T
Molecular Virology, Robert-Koch-Institut, Nordufer 20, 13353 Berlin, Germany. tbuerckstuemmer@cemm.oeaw.ac.at
Kriegs
M
M
Lupberger
J
J
Pauli
E K
EK
Schmittel
S
S
Hildt
E
E
D000818:Animals; D001557:Benzenesulfonates / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011485:Protein Binding; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism; D012093:Replicon; D000077157:Sorafenib; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D034741:RNA, Small Interfering; D017361:Viral Nonstructural Proteins; D009536:Niacinamide; D000077157:Sorafenib; D019908:Proto-Oncogene Proteins c-raf; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase