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

作者：Kawai Yoshinari; Ikeda Masanori^*; Abe Ken ichi; Yano Masahiko; Ariumi Yasuo; Dansako Hiromichi; Yamamoto Kazuhide; Kato Nobuyuki

来源：Hepatology Research, 2009, 39(9): 898-909.

DOI：10.1111/j.1872-034X.2009.00525.x

• cyclosporine A
• hepatitis C virus
• interferon-alpha
• interferon-gamma
• statin

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-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.
Conclusion:
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.

• 出版日期2009-9