title: Hepatitis C virus infection in human liver tissue engrafted in mice with an infectious molecular clone.
abstract: OBJECTIVE
  Recent advances in molecular cloning of hepatitis C virus (HCV) have enabled us to apply some available HCV molecular clones to experimental studies. However, these investigations have been restricted to chimpanzee models or 'isolated hepatocytes' from tree shrews. In this study, we engrafted 'human liver tissue' into immunodeficient mice and investigated HCV infection using an infectious molecular clone.
  
  
  METHODS
  Human liver tissues from normal (non-HCV-infected) liver were transplanted into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. We then inoculated the mice with sera from HCV-infected patients or an infectious HCV molecular clone. HCV RNA was assessed using nested reverse-transcription polymerase chain reaction (PCR), real-time detection PCR and in situ PCR.
  
  
  RESULTS
  Without any growth support, normal human liver tissues survived in NOD/SCID mice while maintaining the original viable hepatic architecture. HCV RNA was detected in the mice serum until the fourth week after the inoculation. In situ PCR and immunohistochemistry clearly demonstrated positive signals for HCV in the cytoplasm of infected hepatocytes, while the engrafted human liver tissues showed no apparent morphological changes indicative of infection.
  
  
  CONCLUSIONS
  Engraftment of human liver tissues into NOD/SCID mice and infection with HCV molecular clones could offer a reverse genetic strategy for HCV infection.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Maeda
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Susumu
authors.initials: S
authors.lastname: Okamoto
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanai
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hata
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Hozumi
authors.forename: Asao
authors.initials: A
authors.lastname: Katsume
authors.forename: Hideko
authors.initials: H
authors.lastname: Nuriya
authors.forename: Jasbir
authors.initials: J
authors.lastname: Sandhu
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ishii
authors.forename: Michinori
authors.initials: M
authors.lastname: Kohara
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000821:virology; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity; D006526:Hepatitis C / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D006824:Hybridization, Genetic; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D016031:Liver Transplantation; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics; D016513:Mice, SCID / Q000235:genetics; D016133:Polymerase Chain Reaction; D020401:Primed In Situ Labeling; D012367:RNA, Viral / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: D012367:RNA, Viral