TY - JOUR
T1 - Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents
AU - Nishimura, Go
AU - Ikeda, Masanori
AU - Mori, Kyoko
AU - Nakazawa, Takahide
AU - Ariumi, Yasuo
AU - Dansako, Hiromichi
AU - Kato, Nobuyuki
N1 - Funding Information:
The authors would like to thank Atsumi Morishita and Takashi Nakamura for their technical assistance. This work was supported by grants-in-aid for a third-term comprehensive 10-year strategy for cancer control and for research on hepatitis from the Ministry of Health, Labor, and Welfare of Japan.
PY - 2009/4
Y1 - 2009/4
N2 - Half of the population of genotype 1 HCV is resistant to current pegylated-interferon-α (PEG-IFN-α) 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-α, IFN-γ, IFN-λ, cyclosporine A, and fluvastatin. Among the replicons, the 1B-4 and KAH5 replicons were the most sensitive and resistant, respectively to IFN-λ (EC50: 1.50 ng/ml vs. 8.50 ng/ml) and fluvastatin (EC50: 2.82 μM vs. 7.87 μM), although these replicons possessed similar features in terms of genetic distance from the O strain, HCV RNA expression levels, and sensitivity to IFN-α (EC50: 1.44 IU/ml vs. 1.37 IU/ml) and cyclosporine A (EC50: 0.71 μg/ml vs. 0.96 μg/ml). These replicons are thus useful tools for examining the mechanism of anti-HCV activity, especially in IFN-λ and statins.
AB - Half of the population of genotype 1 HCV is resistant to current pegylated-interferon-α (PEG-IFN-α) 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-α, IFN-γ, IFN-λ, cyclosporine A, and fluvastatin. Among the replicons, the 1B-4 and KAH5 replicons were the most sensitive and resistant, respectively to IFN-λ (EC50: 1.50 ng/ml vs. 8.50 ng/ml) and fluvastatin (EC50: 2.82 μM vs. 7.87 μM), although these replicons possessed similar features in terms of genetic distance from the O strain, HCV RNA expression levels, and sensitivity to IFN-α (EC50: 1.44 IU/ml vs. 1.37 IU/ml) and cyclosporine A (EC50: 0.71 μg/ml vs. 0.96 μg/ml). These replicons are thus useful tools for examining the mechanism of anti-HCV activity, especially in IFN-λ and statins.
KW - Cyclosporine A
KW - Hepatitis C virus
KW - Interferon-α
KW - Interferon-γ
KW - Interferon-λ
KW - Statin
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U2 - 10.1016/j.antiviral.2009.01.007
DO - 10.1016/j.antiviral.2009.01.007
M3 - Article
C2 - 19428594
AN - SCOPUS:62049083765
VL - 82
SP - 42
EP - 50
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
IS - 1
ER -
