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

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.

Pubmed ID: 17024179

Authors

  • Okamoto T
  • Nishimura Y
  • Ichimura T
  • Suzuki K
  • Miyamura T
  • Suzuki T
  • Moriishi K
  • Matsuura Y

Journal

The EMBO journal

Publication Data

October 18, 2006

Associated Grants

None

Mesh Terms

  • Antiviral Agents
  • Benzoquinones
  • Cell Line, Tumor
  • HSP90 Heat-Shock Proteins
  • Hepacivirus
  • Humans
  • Lactams, Macrocyclic
  • Multiprotein Complexes
  • RNA, Viral
  • Tacrolimus Binding Proteins
  • Viral Nonstructural Proteins
  • Virus Replication