Hepatitis C virus infection in human liver tissue engrafted in mice with an infectious molecular clone

Norio Maeda, Mamoru Watanabe, Susumu Okamoto, Takanori Kanai, Taketo Yamada, Jun Ichi Hata, Nobumichi Hozumi, Asao Katsume, Hideko Nuriya, Jasbir Sandhu, Hiromasa Ishii, Michinori Kohara, Toshifumi Hibi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background/Aims: Recent advances in molecular cloning of hepatitis C virus (HCV) have enabled us to apply some available HCV molecular clones to experimental studies. However, these investigations have been restricted to chimpanzee models or 'isolated hepatocytes' from tree shrews. In this study, we engrafted 'human liver tissue' into immunodeficient mice and investigated HCV infection using an infectious molecular clone. Methods: Human liver tissues from normal (non-HCV-infected) liver were transplanted into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. We then inoculated the mice with sera from HCV-infected patients or an infectious HCV molecular clone. HCV RNA was assessed using nested reverse-transcription polymerase chain reaction (PCR), real-time detection PCR and in situ PCR. Results: Without any growth support, normal human liver tissues survived in NOD/SCID mice while maintaining the original viable hepatic architecture. HCV RNA was detected in the mice serum until the fourth week after the inoculation. In situ PCR and immunohistochemistry clearly demonstrated positive signals for HCV in the cytoplasm of infected hepatocytes, while the engrafted human liver tissues showed no apparent morphological changes indicative of infection. Conclusion: Engraftment of human liver tissues into NOD/SCID mice and infection with HCV molecular clones could offer a reverse genetic strategy for HCV infection.

Original languageEnglish
Pages (from-to)259-267
Number of pages9
JournalLiver International
Volume24
Issue number3
DOIs
Publication statusPublished - 2004 Jun

Keywords

  • Hepatitis C virus
  • Human liver tissue
  • In situ PCR
  • Infectious molecular clone
  • NOD/SCID mouse

ASJC Scopus subject areas

  • Hepatology

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    Maeda, N., Watanabe, M., Okamoto, S., Kanai, T., Yamada, T., Hata, J. I., Hozumi, N., Katsume, A., Nuriya, H., Sandhu, J., Ishii, H., Kohara, M., & Hibi, T. (2004). Hepatitis C virus infection in human liver tissue engrafted in mice with an infectious molecular clone. Liver International, 24(3), 259-267. https://doi.org/10.1111/j.1478-3231.2004.0909.x