title: Development of a hepatitis C virus relapse model using genome-length hepatitis C virus ribonucleic acid-harboring cells possessing the interferon-alpha-resistance phenotype.
abstract: OBJECTIVE
  The cure rate of current interferon (IFN) therapy is limited to approximately 50% and most of the relapses after therapy are caused by genotype-1. To develop a relapse model in cell culture, we attempted to obtain genome-length hepatitis C virus ribonucleic acid (HCV RNA) harboring cells possessing the IFN-alpha-resistance phenotype from previously established OR6 cells, which enabled the luciferase reporter assay for monitoring of HCV RNA replication.
  
  
  METHODS
  The IFN-alpha-resistant HCV RNA-harboring cells and control cells were obtained by the treatment of OR6 cells with and without IFN-alpha, respectively. Then, we examined the relapse of HCV in IFN-alpha-resistant HCV RNA-harboring cells.
  
  
  RESULTS
  Only type I IFN (alpha and beta) showed significantly different anti-HCV activity between IFN-alpha-resistant HCV RNA-harboring cells and control cells. There was no significant difference in the anti-HCV activity of IFN-gamma, fluvastatin, or cyclosporine A between the two types of cells. Furthermore, we showed that fluvastatin or cyclosporine A in combination with IFN-alpha could prevent the relapse after therapy in the IFN-alpha-resistant HCV RNA-harboring cells.
  
  
  CONCLUSIONS
  We developed a HCV relapse model in cell culture using IFN-alpha-resistant HCV RNA-harboring cells. Thus anti-HCV reagents, which have a mechanism different from IFN-alpha, were shown to be useful for preventing a relapse of IFN-alpha-resistant HCV.
authors.affiliation: Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Kawai
authors.forename: Masanori
authors.initials: M
authors.lastname: Ikeda
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Abe
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yano
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ariumi
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Dansako
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kato