title: Establishment of an infectious genotype 1b hepatitis C virus clone in human hepatocyte chimeric mice.
abstract: The establishment of clonal infection of hepatitis C virus (HCV) in a small-animal model is important for the analysis of HCV virology. A previous study developed models of molecularly cloned genotype 1a and 2a HCV infection using human hepatocyte-transplanted chimeric mice. This study developed a new model of molecularly cloned genotype 1b HCV infection. A full-length genotype 1b HCV genome, HCV-KT9, was cloned from a serum sample from a patient with severe acute hepatitis. The chimeric mice were inoculated intrahepatically with in vitro-transcribed HCV-KT9 RNA. Inoculated mice developed viraemia at 2 weeks post-infection, and this persisted for more than 6 weeks. Passage experiments indicated that the sera of these mice contained infectious HCV. Interestingly, a similar clone, HCV-KT1, in which the poly(U/UC) tract was 29 nt shorter than in HCV-KT9, showed poorer in vivo infectivity and replication ability. An in vitro study showed that no virus was produced in the culture medium from HCV-KT9-transfected cells. In conclusion, this study developed a genetically engineered genotype 1b HCV-infected mouse. This mouse model will be useful for the study of HCV virology, particularly the mechanism underlying the variable resistance of HCV genotypes to interferon therapy.
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiraga
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hatakeyama
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Miki
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Chiemi
authors.initials: C
authors.lastname: Noguchi
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Mori
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Fujimoto
authors.affiliation: Research Division, Mitsubishi Tanabe Pharma Corporation, Osaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Iwao
authors.affiliation: Laboratory for Liver Disease, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Laboratory for Liver Disease, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe
authors.affiliation: Laboratory for Liver Disease, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Hirosimakinen-Hospital, Internal Medicine, Hiroshima, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Arataki
authors.affiliation: Developmental Biology Laboratory, Department of Biological Science, Graduate School of Science, Hiroshima University, Higashihiroshima, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Chise
authors.initials: C
authors.lastname: Tateno
authors.affiliation: Developmental Biology Laboratory, Department of Biological Science, Graduate School of Science, Hiroshima University, Higashihiroshima, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yoshizato
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Shinjuku-ku, Japan.
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
authors.affiliation: Laboratory for Liver Disease, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama