TY - JOUR
T1 - A long-awaited small animal model for hepatitis C
AU - Guha, Chandan
AU - Chowdhury, Jayanta Roy
PY - 2002
Y1 - 2002
N2 - Hepatitis C virus replication in mice with chimeric human livers. Mercer DF, Schiller DE, Elliott JF, Douglas DN, Hao C, Rinfret A, Addison WR, Fischer KP, Churchill TA, Lakey JR, Tyrrell DL, Kneteman NM. Surgical-Medical Research Institute, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada. 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 infections prolonged HCV 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 - Hepatitis C virus replication in mice with chimeric human livers. Mercer DF, Schiller DE, Elliott JF, Douglas DN, Hao C, Rinfret A, Addison WR, Fischer KP, Churchill TA, Lakey JR, Tyrrell DL, Kneteman NM. Surgical-Medical Research Institute, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada. 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 infections prolonged HCV 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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U2 - 10.1016/S0168-8278(02)00027-2
DO - 10.1016/S0168-8278(02)00027-2
M3 - Article
C2 - 11867194
AN - SCOPUS:0036185838
SN - 0168-8278
VL - 36
SP - 447
EP - 449
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 3
ER -