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Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis B virus
Author(s) -
Tsuge Masataka,
Hiraga Nobuhiko,
Takaishi Hideki,
Noguchi Chiemi,
Oga Hiromi,
Imamura Michio,
Takahashi Shoichi,
Iwao Eiji,
Fujimoto Yoshifumi,
Ochi Hidenori,
Chayama Kazuaki,
Tateno Chise,
Yoshizato Katsutoshi
Publication year - 2005
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20892
Subject(s) - virology , genetically engineered , hepatocyte , hepatitis b virus , virus , hepatitis virus , biology , genetically modified organism , hepatitis a virus , transgene , gene , genetics , in vitro
Studies of hepatitis B virus (HBV) mutants have been hampered by the lack of a small animal model with long‐term infection of cloned HBV. Using a mouse model in which liver cells were highly replaced with human hepatocytes that survived over a long time with mature human hepatocyte function, we performed transmission experiments of HBV. Human serum containing HBV and the virus produced in HepG2 cell lines that transiently or stably transfected with 1.4 genome length HBV DNA were inoculated. Genetically modified e‐antigen–negative mutant strain also was produced and inoculated into the mouse model. A high‐level (≈10 10 copies/mL) viremia was observed in mice inoculated with HBV‐positive human serum samples. The level of viremia tended to be high in mice with a continuously high human hepatocyte replacement index. High levels and long‐lasting viremia also were observed in mice injected with the in vitro generated HBV. The viremia continued up to 22 weeks until death or killing. Passage experiments showed that the serum of these mice contained infectious HBV. Genetically engineered hepatitis B e antigen–negative mutant clone also was shown to be infectious. Lamivudine effectively reduced the level of viremia in these infected mice. In conclusion , this mouse model of HBV infection is a useful tool for the study of HBV virology and evaluation of anti‐HBV drugs. Our results indicate that HBeAg is dispensable for active viral production and transmission. (H EPATOLOGY 2005;42:1046–1054.)