Development of a hepatitis C virus relapse model using genome-length hepatitis C virus ribonucleic acid-harboring cells possessing the interferon-α-resistance phenotype

Yoshinari Kawai, Masanori Ikeda, Ken Ichi Abe, Masahiko Yano, Yasuo Ariumi, Hiromichi Dansako, Kazuhide Yamamoto, Nobuyuki Kato

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Aim: 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-α-resistance phenotype from previously established OR6 cells, which enabled the luciferase reporter assay for monitoring of HCV RNA replication. Methods: The IFN-α-resistant HCV RNA-harboring cells and control cells were obtained by the treatment of OR6 cells with and without IFN-α, respectively. Then, we examined the relapse of HCV in IFN-α-resistant HCV RNA-harboring cells. Results: Only type I IFN(αand β) showed significantly different anti-HCV activity between IFN-α-resistant HCV RNA-harboring cells and control cells. There was no significant difference in the anti-HCV activity of IFN-γ, fluvastatin, or cyclosporine A between the two types of cells. Furthermore, we showed that fluvastatin or cyclosporine A in combination with IFN-α could prevent the relapse after therapy in the IFN-α-resistant HCV RNA-harboring cells. Conclusion: We developed a HCV relapse model in cell culture using IFN-α-resistant HCV RNA-harboring cells. Thus anti-HCV reagents, which have a mechanism different from IFN-α, were shown to be useful for preventing a relapse of IFN-α-resistant HCV.

Original languageEnglish
Pages (from-to)898-909
Number of pages12
JournalHepatology Research
Volume39
Issue number9
DOIs
Publication statusPublished - 2009

Keywords

  • Cyclosporine A
  • Hepatitis C virus
  • Interferon-α
  • Interferon-γ
  • Statin

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

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