Establishment of an infectious genotype 1b hepatitis C virus clone in human hepatocyte chimeric mice
Kimura, Takashi and Imamura, Michio and Hiraga, Nobuhiko and Hatakeyama, Tsuyoshi and Miki, Daiki and Noguchi, Chiemi and Mori, Nami and Tsuge, Masataka and Takahashi, Shoichi and Fujimoto, Yoshifumi and Iwao, Eiji and Ochi, Hidenori and Abe, Hiromi and Maekawa, Toshiro and Arataki, Keiko and Tateno, Chise and Yoshizato, Katsutoshi and Wakita, Takaji and Okamoto, Toru and Matsuura, Yoshiharu and Chayama, Kazuaki,, 89, 2108-2113 (2008),
doi = https://doi.org/10.1099/vir.0.83658-0,
publicationName = Microbiology Society,
issn = 0022-1317,
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.,
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