Premium
Raf‐1 kinase associates with Hepatitis C virus NS5A and regulates viral replication
Author(s) -
Bürckstümmer T.,
Kriegs M.,
Lupberger J.,
Pauli E.K.,
Schmittel S.,
Hildt E.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.12.071
Subject(s) - ns5a , virology , hepatitis c virus , viral replication , viral transformation , biology , ns2 3 protease , protein kinase r , kinase , virus , protein kinase a , hepacivirus , microbiology and biotechnology , mitogen activated protein kinase kinase
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.