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  • Title: Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents.
    Author: Nishimura G, Ikeda M, Mori K, Nakazawa T, Ariumi Y, Dansako H, Kato N.
    Journal: Antiviral Res; 2009 Apr; 82(1):42-50. PubMed ID: 19428594.
    Abstract:
    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 1 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 (O 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 (EC(50): 1.50 ng/ml vs. 8.50 ng/ml) and fluvastatin (EC(50): 2.82 microM vs. 7.87 microM), although these replicons possessed similar features in terms of genetic distance from the O strain, HCV RNA expression levels, and sensitivity to IFN-alpha (EC(50): 1.44 IU/ml vs. 1.37 IU/ml) and cyclosporine A (EC(50): 0.71 microg/ml vs. 0.96 microg/ml). These replicons are thus useful tools for examining the mechanism of anti-HCV activity, especially in IFN-lambda and statins.
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