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Amino acid substitutions of hepatitis C virus core protein are not associated with intracellular antiviral response to interferon-α in vitro

Authors

  • Fusao Ikeda,

    1. Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
    2. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
    3. Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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  • Hiromichi Dansako,

    1. Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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  • Go Nishimura,

    1. Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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  • Kyoko Mori,

    1. Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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  • Yoshinari Kawai,

    1. Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
    2. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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  • Yasuo Ariumi,

    1. Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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  • Yasuhiro Miyake,

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
    2. Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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  • Akinobu Takaki,

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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  • Kazuhiro Nouso,

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
    2. Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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  • Yoshiaki Iwasaki,

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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  • Masanori Ikeda,

    1. Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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  • Nobuyuki Kato,

    1. Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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  • Kazuhide Yamamoto

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
    2. Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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Correspondence
Fusao Ikeda, MD, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558, Japan
Tel: +81 86 235 7219
Fax: +81 86 225 5991
e-mail: fikeda@md.okayama-u.ac.jp

Abstract

Background: Studies on patients with hepatitis C virus (HCV) of genotype 1b have suggested that amino acids (aa) 70 and/or 91 of the HCV core protein affect the outcome of interferon (IFN)-α and ribavirin (RBV) therapy, although there are no clear supporting data in vitro.

Aims: This study was designed to determine the differences among the antiviral activities of HCV core proteins with various substitutions at aa70 and/or aa91.

Methods: The retroviral vectors expressing the HCV core proteins with substitutions of arginine/leucine, arginine/methionine, glutamine/leucine or glutamine/methionine at aa70/aa91 were transiently transfected or stably transducted into an immortalized hepatocyte line (PH5CH8), hepatoma cell lines and an HCV-RNA replicating cell line (sOR) to evaluate antiviral responses to IFN-α or IFN-α/RBV. Sequence analysis was performed using genome-length HCV-RNA replicating cells (OR6 and AH1) to evaluate HCV core mutations during IFN-α treatment.

Results: The promoter activity levels of IFN-stimulated genes in the transiently transfected cells or the mRNA levels of 2′-5′-oligoadenylate synthetase in the stably transducted PH5CH8 cells were not associated with the HCV core aa70 and/or aa91 substitutions during IFN-α treatment. Antiviral responses to IFN-α or IFN-α/RBV treatment were enhanced in sOR cells stably transducted with the HCV core, although there were no differences in antiviral responses among the cells expressing different core types. Sequence analysis showed no aa mutations after IFN-α treatment.

Conclusions: Antiviral activities were enhanced by HCV core transduction, but they were not associated with the HCV core aa70 and/or aa91 substitutions by in vitro analysis.

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