Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 42-50 |
| Number of pages | 9 |
| Journal | Antiviral Research |
| Volume | 82 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Apr 2009 |
Fingerprint
Keywords
- Cyclosporine A
- Hepatitis C virus
- Interferon-α
- Interferon-γ
- Interferon-λ
- Statin
ASJC Scopus subject areas
- Virology
- Pharmacology
Cite this
Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents. / Nishimura, Go; Ikeda, Masanori; Mori, Kyoko; Nakazawa, Takahide; Ariumi, Yasuo; Dansako, Hiromichi; Kato, Nobuyuki.
In: Antiviral Research, Vol. 82, No. 1, 04.2009, p. 42-50.Research output: Contribution to journal › Article
}
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
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
UR - http://www.scopus.com/inward/record.url?scp=62049083765&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=62049083765&partnerID=8YFLogxK
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 -