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

详细信息    查看全文

• 作者：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 ; Kazuaki Chayama ; et al.
• 关键词：ALT ; alanine aminotransferase ; GCV ; ganciclovir ; HBV ; hepatitis B virus ; HCV ; hepatitis C virus ; HSA ; human serum albumin ; HSVtk ; herpes simplex virus type-1 thymidine kinase ; IFN ; interferon ; PegIFN-alpha ; pegylated interferon-alpha ; RI ; repopulation index ; RT-PCR ; reverse transcript-polymerase chain reaction ; SCID ; severe combined immunodeficiency ; uPA ; urokinase-type plasminogen activator
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：8 November, 2013
• 年：2013
• 卷：441
• 期：1
• 页码：230-235
• 全文大小：1172 K

文摘

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.