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

701 Citations (Scopus)

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 - Aug 29 2001

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Virus Replication
Viruses
Hepacivirus
Liver
Hepatocytes
Plasminogen Activators
Viral RNA
Viral Proteins
Antiviral Agents
Animals
SCID Mice
Virus Diseases
Infection
Viral Load
Transgenes
Virion
Animal Models
Serum

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mercer, D. F., Schiller, D. E., Elliott, J. F., Douglas, D. N., Hao, C., Rinfret, A., ... 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

Hepatitis C virus replication in mice with chimeric human livers. / Mercer, David F.; Schiller, Daniel E.; Elliott, John F.; Douglas, Donna N.; Hao, Chunhai; Rinfret, Aline; Addison, William R.; Fischer, Karl P.; Churchill, Thomas A.; Lakey, Jonathan R.T.; Tyrrell, David L.J.; Kneteman, Norman M.

In: Nature Medicine, Vol. 7, No. 8, 29.08.2001, p. 927-933.

Research output: Contribution to journalArticle

Mercer, DF, Schiller, DE, Elliott, JF, Douglas, DN, Hao, C, Rinfret, A, Addison, WR, Fischer, KP, Churchill, TA, Lakey, JRT, Tyrrell, DLJ & Kneteman, NM 2001, 'Hepatitis C virus replication in mice with chimeric human livers', Nature Medicine, vol. 7, no. 8, pp. 927-933. https://doi.org/10.1038/90968
Mercer DF, Schiller DE, Elliott JF, Douglas DN, Hao C, Rinfret A et al. Hepatitis C virus replication in mice with chimeric human livers. Nature Medicine. 2001 Aug 29;7(8):927-933. https://doi.org/10.1038/90968
Mercer, David F. ; Schiller, Daniel E. ; Elliott, John F. ; Douglas, Donna N. ; Hao, Chunhai ; Rinfret, Aline ; Addison, William R. ; Fischer, Karl P. ; Churchill, Thomas A. ; Lakey, Jonathan R.T. ; Tyrrell, David L.J. ; Kneteman, Norman M. / Hepatitis C virus replication in mice with chimeric human livers. In: Nature Medicine. 2001 ; Vol. 7, No. 8. pp. 927-933.
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