Hepatitis C virus replication in mice with chimeric human livers

David F. Mercer, Daniel E. Schiller, John F. Elliott, Donna N. Douglas, Chunhai Hao, Aline Rinfret, William R. Addison, Karl P. Fischer, Thomas A. Churchill, Jonathan R.T. Lakey, David L.J. Tyrrell, Norman M. Kneteman

Research output: Contribution to journalArticle

710 Scopus citations

Abstract

Lack of a small animal model of the human hepatitis C virus (HCV) has impeded development of antiviral therapies against this epidemic infection. By transplanting normal human hepatocytes into SCID mice carrying a plasminogen activator transgene (Alb-uPA), we generated mice with chimeric human livers. Homozygosity of Alb-uPA was associated with significantly higher levels of human hepatocyte engraftment, and these mice developed prolonged HCV infections with high viral titers after inoculation with infected human serum. Initial increases in total viral load were up to 1950-fold, with replication confirmed by detection of negative-strand viral RNA in transplanted livers. HCV viral proteins were localized to human hepatocyte nodules, and infection was serially passaged through three generations of mice confirming both synthesis and release of infectious viral particles. These chimeric mice represent the first murine model suitable for studying the human hepatitis C virus in vivo.

Original languageEnglish (US)
Pages (from-to)927-933
Number of pages7
JournalNature Medicine
Volume7
Issue number8
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Hepatitis C virus replication in mice with chimeric human livers'. Together they form a unique fingerprint.

  • Cite this

    Mercer, D. F., Schiller, D. E., Elliott, J. F., Douglas, D. N., Hao, C., Rinfret, A., Addison, W. R., Fischer, K. P., Churchill, T. A., Lakey, J. R. T., Tyrrell, D. L. J., & Kneteman, N. M. (2001). Hepatitis C virus replication in mice with chimeric human livers. Nature Medicine, 7(8), 927-933. https://doi.org/10.1038/90968