Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis C virus and its susceptibility to interferon

We developed a reverse genetics system of hepatitis C virus (HCV) genotypes 1a and 2a using infectious clones and human hepatocyte chimeric mice. We inoculated cell culture-produced genotype 2a (JFH-1) HCV intravenously. We also injected genotype 1a CV-H77C clone RNA intrahepatically. Mice inoculate...

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Bibliographic Details
Published in:FEBS letters 2007-05, Vol.581 (10), p.1983-1987
Main Authors: Hiraga, Nobuhiko, Imamura, Michio, Tsuge, Masataka, Noguchi, Chiemi, Takahashi, Shoichi, Iwao, Eiji, Fujimoto, Yoshifumi, Abe, Hiromi, Maekawa, Toshiro, Ochi, Hidenori, Tateno, Chise, Yoshizato, Katsutoshi, Sakai, Akihito, Sakai, Yoshio, Honda, Masao, Kaneko, Shuichi, Wakita, Takaji, Chayama, Kazuaki
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Chimera - virology
Clone Cells
Genetic Engineering
Genotype
HBV
HCV
HCV RNA
Hepacivirus - drug effects
Hepacivirus - genetics
Hepacivirus - physiology
hepatitis B virus
Hepatitis C - virology
Hepatitis C virus
Hepatocytes - drug effects
Hepatocytes - transplantation
Hepatocytes - virology
HSA
Human hepatocyte chimeric mouse
Human serum albumin
Humans
IFN
Interferon
Interferon-alpha - pharmacology
Mice
RNA, Viral - blood
SCID, severe combined immunodeficiency
Serial Passage
Serum Albumin
Transcription, Genetic - drug effects
uPA
urokinase-type plasminogen activator
Viral Load
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Description
Summary:We developed a reverse genetics system of hepatitis C virus (HCV) genotypes 1a and 2a using infectious clones and human hepatocyte chimeric mice. We inoculated cell culture-produced genotype 2a (JFH-1) HCV intravenously. We also injected genotype 1a CV-H77C clone RNA intrahepatically. Mice inoculated with HCV by both procedures developed measurable and transmissible viremia. Interferon (IFN) alpha treatment resulted in greater reduction of genotype 2a HCV levels than genotype 1a, as seen in clinical practice. Genetically engineered HCV infection system should be useful for analysis of the mechanisms of resistance of HCV to IFN and other drugs.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2007.04.021