Establishment of an infectious genotype 1b hepatitis C virus clone in human hepatocyte chimeric mice.
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.
Kimura
Takashi
T
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.
Imamura
Michio
M
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.
Hiraga
Nobuhiko
N
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.
Hatakeyama
Tsuyoshi
T
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.
Miki
Daiki
D
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.
Noguchi
Chiemi
C
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.
Mori
Nami
N
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.
Tsuge
Masataka
M
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.
Takahashi
Shoichi
S
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.
Fujimoto
Yoshifumi
Y
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.
Iwao
Eiji
E
Research Division, Mitsubishi Tanabe Pharma Corporation, Osaka, Japan.
Ochi
Hidenori
H
Laboratory for Liver Disease, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
Abe
Hiromi
H
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.
Maekawa
Toshiro
T
Laboratory for Liver Disease, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
Arataki
Keiko
K
Hirosimakinen-Hospital, Internal Medicine, Hiroshima, Japan.
Tateno
Chise
C
Developmental Biology Laboratory, Department of Biological Science, Graduate School of Science, Hiroshima University, Higashihiroshima, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
Yoshizato
Katsutoshi
K
Developmental Biology Laboratory, Department of Biological Science, Graduate School of Science, Hiroshima University, Higashihiroshima, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
Wakita
Takaji
T
Department of Virology II, National Institute of Infectious Diseases, Shinjuku-ku, Japan.
Okamoto
Toru
T
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Matsuura
Yoshiharu
Y
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Chayama
Kazuaki
K
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.