A novel TK-NOG based humanized mouse model for the study of HBV and HCV infections.

HBV及びHCV感染症研究のための新たなTK-NOGベースヒト化マウスモデルの検討

Kosaka Keiichi

The immunodeficient mice transplanted with human hepatocytes are available for the study of the human hepatitis viruses. Recently, human hepatocytes were also successfully transplanted in herpes simplex virus type-1 thymidine kinase (TK)-NOG mice. In this study, we attempted to infect hepatitis virus in humanized TK-NOG mice and urokinase-type plasminogen activator-severe combined immunodeficiency (uPA-SCID) mice. TK-NOG mice were injected intraperitoneally with 6 mg/kg of ganciclovir (GCV), and transplanted with human hepatocytes. Humanized TK-NOG mice and uPA/SCID mice were injected with hepatitis B virus (HBV)- or hepatitis C virus (HCV)-positive human serum samples. Human hepatocyte repopulation index (RI) estimated from human serum albumin levels in TK-NOG mice correlated well with pre-transplantation serum ALT levels induced by ganciclovir treatment. All humanized TK-NOG and uPA-SCID mice injected with HBV infected serum developed viremia irrespective of lower replacement index. In contrast, establishment of HCV viremia was significantly more frequent in TK-NOG mice with low human hepatocyte RI (<70%) than uPA-SCID mice with similar RI. Frequency of mice spontaneously in early stage of viral infection experiment (8 weeks after injection) was similar in both TK-NOG mice and uPA-SCID mice. Effects of drug treatment with entecavir or interferon were similar in both mouse models. TK-NOG mice thus useful for study of hepatitis virus virology and evaluation of anti-viral drugs.

Human hepatocyte chimeric mouse

TK-NOG mouse

uPA-SCID mouse

Hepatitis B virus

Hepatitis C virus

Human serum albumin

Medical sciences [ 490 ]

jpn

Keiichi Kosaka, Nobuhiko Hiraga, Michio Imamura, Satoshi Yoshimi, Eisuke Murakami, Takashi Nakahara, Yoji Honda, Atsushi Ono, Tomokazu Kawaoka, Masataka Tsuge, Hiromi Abe, C. Nelson Hayes, Daiki Miki, Hiroshi Aikata, Hidenori Ochi, Yuji Ishida, Chise Tateno, Katsutoshi Yoshizato, Tamito Sasaki and Kazuaki Chayama; A novel TK-NOG based humanized mouse model for the study of HBV and HCV infections; Biochemical and Biophysical Research Communications, Volume 441, Issue 1, 8 November 2013, Pages 230-235 (doi: 10.1016/j.bbrc.2013.10.040) references

[DOI] http://doi.org/10.1016/j.bbrc.2013.10.040 references

広島大学