Bürckstümmer T, Kriegs M, Lupberger J, Pauli E K, Schmittel S, Hildt E
Molecular Virology, Robert-Koch-Institut, Nordufer 20, 13353 Berlin, Germany.
FEBS Lett. 2006 Jan 23;580(2):575-80. doi: 10.1016/j.febslet.2005.12.071. Epub 2005 Dec 29.
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.
丙型肝炎病毒（HCV）是一种正链RNA病毒，常导致与严重肝脏疾病相关的持续性感染。HCV非结构蛋白5A（NS5A）对病毒复制至关重要。在此，激酶Raf-1被鉴定为NS5A的一种新型细胞结合伴侣，与NS5A的C末端结构域结合。Raf-1与NS5A在HCV复制复合物中共定位。NS5A与Raf-1的相互作用导致Raf-1在丝氨酸338处的磷酸化增加。Raf-1的完整性对HCV复制至关重要：小分子抑制剂BAY43-9006对Raf-1的抑制或siRNA对Raf-1的下调会减弱病毒复制。
