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

• Published in: Biochemical and biophysical research communications 2013-11, Vol.441 (1), p.230-235
• Main Authors: Kosaka, Keiichi, Hiraga, Nobuhiko, Imamura, Michio, Yoshimi, Satoshi, Murakami, Eisuke, Nakahara, Takashi, Honda, Yoji, Ono, Atsushi, Kawaoka, Tomokazu, Tsuge, Masataka, Abe, Hiromi, Hayes, C. Nelson, Miki, Daiki, Aikata, Hiroshi, Ochi, Hidenori, Ishida, Yuji, Tateno, Chise, Yoshizato, Katsutoshi, Sasaki, Tamito, Chayama, Kazuaki
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Animals; Antiviral Agents - pharmacology; Disease Models, Animal; Ganciclovir - administration & dosage; Ganciclovir - pharmacology; Hepacivirus - drug effects; Hepatitis B - blood; Hepatitis B - enzymology; Hepatitis B - pathology; Hepatitis B - virology; Hepatitis B virus; Hepatitis B virus - drug effects; Hepatitis C - blood; Hepatitis C - enzymology; Hepatitis C - pathology; Hepatitis C - virology; Hepatitis C virus; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatocytes - pathology; Herpes simplex virus; Human hepatocyte chimeric mouse; Human serum albumin; Humans; Mice; Mice, SCID; Mice, Transgenic; Survival Analysis; Thymidine Kinase - metabolism; TK-NOG mouse; uPA–SCID mouse; Urokinase-Type Plasminogen Activator - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.10.040

•TK-NOG mice with humanized livers are available for hepatitis viruses infection.•The infectiveness with hepatitis viruses is as well or better than uPA/SCID mice.•Humanized TK-NOG mouse is a useful animal model for the study of hepatitis viruses. 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 6mg/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 (