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

doi:10.1038/90968

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

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788 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 language	English (US)
Pages (from-to)	927-933
Number of pages	7
Journal	Nature Medicine
Volume	7
Issue number	8
DOIs	https://doi.org/10.1038/90968
State	Published - 2001
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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@article{7117a2dc141c412c8564395d8c5799bc,

title = "Hepatitis C virus replication in mice with chimeric human livers",

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.",

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

year = "2001",

doi = "10.1038/90968",

language = "English (US)",

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pages = "927--933",

journal = "Nature Medicine",

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T1 - Hepatitis C virus replication in mice with chimeric human livers

AU - Mercer, David F.

AU - Schiller, Daniel E.

AU - Elliott, John F.

AU - Douglas, Donna N.

AU - Hao, Chunhai

AU - Rinfret, Aline

AU - Addison, William R.

AU - Fischer, Karl P.

AU - Churchill, Thomas A.

AU - Lakey, Jonathan R.T.

AU - Tyrrell, David L.J.

AU - Kneteman, Norman M.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

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Hepatitis C virus replication in mice with chimeric human livers

Abstract

ASJC Scopus subject areas

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