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.
authors.affiliation: Surgical-Medical Research Institute, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: D F
authors.initials: DF
authors.lastname: Mercer
authors.forename: D E
authors.initials: DE
authors.lastname: Schiller
authors.forename: J F
authors.initials: JF
authors.lastname: Elliott
authors.forename: D N
authors.initials: DN
authors.lastname: Douglas
authors.forename: C
authors.initials: C
authors.lastname: Hao
authors.forename: A
authors.initials: A
authors.lastname: Rinfret
authors.forename: W R
authors.initials: WR
authors.lastname: Addison
authors.forename: K P
authors.initials: KP
authors.lastname: Fischer
authors.forename: T A
authors.initials: TA
authors.lastname: Churchill
authors.forename: J R
authors.initials: JR
authors.lastname: Lakey
authors.forename: D L
authors.initials: DL
authors.lastname: Tyrrell
authors.forename: N M
authors.initials: NM
authors.lastname: Kneteman
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D002678:Chimera; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006720:Homozygote; D006801:Humans; D008099:Liver / Q000821:virology*; D051379:Mice; D016513:Mice, SCID; D012367:RNA, Viral / Q000302:isolation & purification; D019076:Transgenes; D014779:Virus Replication
chemical_list: D012367:RNA, Viral