Virus Genes

, Volume 44, Issue 3, pp 374–381 | Cite as

Development of a drug assay system with hepatitis C virus genome derived from a patient with acute hepatitis C

  • Kyoko Mori
  • Youki Ueda
  • Yasuo Ariumi
  • Hiromichi Dansako
  • Masanori Ikeda
  • Nobuyuki Kato


We developed a new cell culture drug assay system (AH1R), in which genome-length hepatitis C virus (HCV) RNA (AH1 strain of genotype 1b derived from a patient with acute hepatitis C) efficiently replicates. By comparing the AH1R system with the OR6 assay system that we developed previously (O strain of genotype 1b derived from an HCV-positive blood donor), we demonstrated that the anti-HCV profiles of reagents including interferon-γ and cyclosporine A significantly differed between these assay systems. Furthermore, we found unexpectedly that rolipram, an anti-inflammatory drug, showed anti-HCV activity in the AH1R assay but not in the OR6 assay, suggesting that the anti-HCV activity of rolipram differs depending on the HCV strain. Taken together, these results suggest that the AH1R assay system is useful for the objective evaluation of anti-HCV reagents and for the discovery of different classes of anti-HCV reagents.


HCV Acute hepatitis C Anti-HCV drug assay system Anti-HCV activity of rolipram 



This study was supported by grants-in-aid for research on hepatitis from the Ministry of Health, Labor, and Welfare of Japan. K. M. was supported by a Research Fellowship for Young Scientists from the Japan Society for the Promotion of Science.


  1. 1.
    N. Kato, Acta Med. Okayama 55, 133–159 (2001)PubMedGoogle Scholar
  2. 2.
    N. Kato, M. Hijikata, Y. Ootsuyama, M. Nakagawa, S. Ohkoshi, T. Sugimura, K. Shimotohno, Proc. Natl. Acad. Sci. USA 87, 9524–9528 (1990)PubMedCrossRefGoogle Scholar
  3. 3.
    R. Bartenschlager, S. Sparacio, Virus Res. 127, 195–207 (2007)PubMedCrossRefGoogle Scholar
  4. 4.
    D. Moradpour, F. Penin, C.M. Rice, Nat. Rev. Microbiol. 5, 453–463 (2007)PubMedCrossRefGoogle Scholar
  5. 5.
    V. Lohmann, F. Korner, J. Koch, U. Herian, L. Theilmann, R. Bartenschlager, Science 285, 110–113 (1999)PubMedCrossRefGoogle Scholar
  6. 6.
    M. Ikeda, N. Kato, Adv. Drug Deliv. Rev. 59, 1277–1289 (2007)PubMedCrossRefGoogle Scholar
  7. 7.
    M. Ikeda, K. Abe, H. Dansako, T. Nakamura, K. Naka, N. Kato, Biochem. Biophys. Res. Commun. 329, 1350–1359 (2005)PubMedCrossRefGoogle Scholar
  8. 8.
    K. Naka, M. Ikeda, K. Abe, H. Dansako, N. Kato, Biochem. Biophys. Res. Commun. 330, 871–879 (2005)PubMedCrossRefGoogle Scholar
  9. 9.
    M. Ikeda, K. Abe, M. Yamada, H. Dansako, K. Naka, N. Kato, Hepatology 44, 117–125 (2006)PubMedCrossRefGoogle Scholar
  10. 10.
    A. Nozaki, M. Morimoto, M. Kondo, T. Oshima, K. Numata, S. Fujisawa, T. Kaneko, E. Miyajima, S. Morita, K. Mori, M. Ikeda, N. Kato, K. Tanaka, Arch. Virol. 155, 601–605 (2010)PubMedCrossRefGoogle Scholar
  11. 11.
    M. Ikeda, Y. Kawai, K. Mori, M. Yano, K. Abe, G. Nishimura, H. Dansako, Y. Ariumi, T. Wakita, K. Yamamoto, N. Kato, Liver Int. 31, 871–880 (2011)PubMedCrossRefGoogle Scholar
  12. 12.
    K. Mori, K. Abe, H. Dansako, Y. Ariumi, M. Ikeda, N. Kato, Biochem. Biophys. Res. Commun. 371, 104–109 (2008)PubMedCrossRefGoogle Scholar
  13. 13.
    N. Kato, K. Sugiyama, K. Namba, H. Dansako, T. Nakamura, M. Takami, K. Naka, A. Nozaki, K. Shimotohno, Biochem. Biophys. Res. Commun. 306, 756–766 (2003)PubMedCrossRefGoogle Scholar
  14. 14.
    K. Mori, M. Ikeda, Y. Ariumi, H. Dansako, T. Wakita, N. Kato, Virus Res. 157, 61–70 (2011)PubMedCrossRefGoogle Scholar
  15. 15.
    N. Kato, K. Mori, K. Abe, H. Dansako, M. Kuroki, Y. Ariumi, T. Wakita, M. Ikeda, Virus Res. 146, 41–50 (2009)PubMedCrossRefGoogle Scholar
  16. 16.
    S.J. MacKenzie, M.D. Houslay, Biochem. J. 347, 571–578 (2000)PubMedCrossRefGoogle Scholar
  17. 17.
    M. Yano, M. Ikeda, K. Abe, H. Dansako, S. Ohkoshi, Y. Aoyagi, N. Kato, Antimicrob. Agents Chemother. 51, 2016–2027 (2007)PubMedCrossRefGoogle Scholar
  18. 18.
    G. Nishimura, M. Ikeda, K. Mori, T. Nakazawa, Y. Ariumi, H. Dansako, N. Kato, Antiviral Res. 82, 42–50 (2009)PubMedCrossRefGoogle Scholar
  19. 19.
    P. Gastaminza, C. Whitten-Baue, F.V. Chisari, Proc. Natl. Acad. Sci. USA 107, 291–296 (2010)PubMedCrossRefGoogle Scholar
  20. 20.
    N. Enomoto, I. Sakuma, Y. Asahina, M. Kurosaki, T. Murakami, C. Yamamoto, Y. Ogura, N. Izumi, F. Marumo, C. Sato, N. Engl. J. Med. 334, 77–81 (1996)PubMedCrossRefGoogle Scholar
  21. 21.
    N. Akuta, F. Suzuki, Y. Kawamura, H. Yatsuji, H. Sezaki, Y. Suzuki, T. Hosaka, M. Kobayashi, M. Kobayashi, Y. Arase, K. Ikeda, H. Kumada, J. Med. Virol. 79, 1686–1695 (2007)PubMedCrossRefGoogle Scholar
  22. 22.
    S. Togo, X. Liu, X. Wang, Am. J. Physiol. Lung Cell. Mol. Physiol. 296, L959–L969 (2009)PubMedCrossRefGoogle Scholar
  23. 23.
    W. Lin, W.L. Tsai, R.X. Shao, G. Wu, L.F. Peng, L.L. Barlow, W.J. Chung, L. Zhang, H. Zhao, J.Y. Jang, R.T. Chung, Gastroenterology 138, 2509–2518 (2010)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Kyoko Mori
    • 1
  • Youki Ueda
    • 1
  • Yasuo Ariumi
    • 1
  • Hiromichi Dansako
    • 1
  • Masanori Ikeda
    • 1
  • Nobuyuki Kato
    • 1
  1. 1.Department of Tumor VirologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesOkayamaJapan

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