Hepatitis C virus infection in human liver tissue engrafted in mice with an infectious molecular clone
Article first published online: 9 JUN 2004
Volume 24, Issue 3, pages 259–267, June 2004
How to Cite
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. and Hibi, T. (2004), Hepatitis C virus infection in human liver tissue engrafted in mice with an infectious molecular clone. Liver International, 24: 259–267. doi: 10.1111/j.1478-3231.2004.0909.x
- Issue published online: 9 JUN 2004
- Article first published online: 9 JUN 2004
- Received 18 July 2003,accepted 4 February 2004
- hepatitis C virus;
- human liver tissue;
- infectious molecular clone;
- in situ PCR;
- NOD/SCID mouse
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.