Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90.

Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
The EMBO Journal (Impact Factor: 10.75). 11/2006; 25(20):5015-25. DOI: 10.1038/sj.emboj.7601367
Source: PubMed

ABSTRACT Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a component of viral replicase and is well known to modulate the functions of several host proteins. Here, we show that NS5A specifically interacts with FKBP8, a member of the FK506-binding protein family, but not with other homologous immunophilins. Three sets of tetratricopeptide repeats in FKBP8 are responsible for interactions with NS5A. The siRNA-mediated knockdown of FKBP8 in a human hepatoma cell line harboring an HCV RNA replicon suppressed HCV RNA replication, and this reduction was reversed by the expression of an siRNA-resistant FKBP8 mutant. Furthermore, immunoprecipitation analyses revealed that FKBP8 forms a complex with Hsp90 and NS5A. Treatment of HCV replicon cells with geldanamycin, an inhibitor of Hsp90, suppressed RNA replication in a dose-dependent manner. These results suggest that the complex consisting of NS5A, FKBP8, and Hsp90 plays an important role in HCV RNA replication.


Available from: Kohji Moriishi, Jun 03, 2015
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