Journal
ANTIVIRAL RESEARCH
Volume 82, Issue 1, Pages 42-50Publisher
ELSEVIER
DOI: 10.1016/j.antiviral.2009.01.007
Keywords
Hepatitis C virus; Interferon-alpha; Interferon-gamma; Interferon-lambda; Cyclosporine A; Statin
Categories
Funding
- Ministry of Health, Labor, and Welfare of Japan
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Half of the population of genotype 1 HCV is resistant to current pegylated-interferon-alpha (PEG-IFN-alpha) and ribavirin therapy. The resistance to IFN therapy is an urgent problem, especially in patients with genotype I HCV infection. However, sensitivities among HCV strains to anti-HCV reagents including IFNs have not been thoroughly addressed. Here, we established three different subgenomic replicons (1B-4, 1B-5, and KAH5 strains) in addition to our previously established replicon (0 strain). We comparatively examined the sensitivities of four replicons to IFN-alpha, IFN-gamma, IFN-lambda, cyclosporine A, and fluvastatin. Among the replicons, the 1B-4 and KAH5 replicons were the most sensitive and resistant, respectively to IFN-lambda (EC50: 1.50 ng/ml vs. 8.50 ng/ml) and fluvastatin (EC50: 2.82 mu M vs. 7.87 mu M), although these replicons possessed similar features in terms of genetic distance from the 0 strain, HCV RNA expression levels, and sensitivity to IFN-alpha (EC50: 1.44 IU/ml vs. 1.37 IU/ml) and cyclosporine A (EC50: 0.71 mu g/ml vs. 0.96 mu g/ml). These replicons are thus useful tools for examining the mechanism of anti-HCV activity, especially in IFN-lambda and statins. (C) 2009 Elsevier B.V. All rights reserved.
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