Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents

Go Nishimura, Masanori Ikeda, Kyoko Mori, Takahide Nakazawa, Yasuo Ariumi, Hiromichi Dansako, Nobuyuki Kato

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 languageEnglish
Pages (from-to)42-50
Number of pages9
JournalAntiviral Research
Volume82
Issue number1
DOIs
Publication statusPublished - Apr 2009

Fingerprint

Replicon
Genotype
fluvastatin
Serum
Cyclosporine
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Ribavirin
Interferons
RNA
Therapeutics
Infection
Population

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 journalArticle

Nishimura, Go ; Ikeda, Masanori ; Mori, Kyoko ; Nakazawa, Takahide ; Ariumi, Yasuo ; Dansako, Hiromichi ; Kato, Nobuyuki. / Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents. In: Antiviral Research. 2009 ; Vol. 82, No. 1. pp. 42-50.
@article{78674e3294da403e82cf00dfddeb78fa,
title = "Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents",
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.",
keywords = "Cyclosporine A, Hepatitis C virus, Interferon-α, Interferon-γ, Interferon-λ, Statin",
author = "Go Nishimura and Masanori Ikeda and Kyoko Mori and Takahide Nakazawa and Yasuo Ariumi and Hiromichi Dansako and Nobuyuki Kato",
year = "2009",
month = "4",
doi = "10.1016/j.antiviral.2009.01.007",
language = "English",
volume = "82",
pages = "42--50",
journal = "Antiviral Research",
issn = "0166-3542",
publisher = "Elsevier",
number = "1",

}

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 -