title: A novel TK-NOG based humanized mouse model for the study of HBV and HCV infections.
abstract: 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 (8weeks 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.
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan; Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kosaka
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiraga
authors.forename: Michio
authors.initials: M
authors.lastname: Imamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshimi
authors.forename: Eisuke
authors.initials: E
authors.lastname: Murakami
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakahara
authors.forename: Yoji
authors.initials: Y
authors.lastname: Honda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ono
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Kawaoka
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe
authors.forename: C Nelson
authors.initials: CN
authors.lastname: Hayes
authors.forename: Daiki
authors.initials: D
authors.lastname: Miki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aikata
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishida
authors.forename: Chise
authors.initials: C
authors.lastname: Tateno
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yoshizato
authors.forename: Tamito
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D015774:Ganciclovir / Q000008:administration & dosage / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects; D006509:Hepatitis B / Q000097:blood / Q000201:enzymology / Q000473:pathology* / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects; D006526:Hepatitis C / Q000097:blood / Q000201:enzymology / Q000473:pathology* / Q000821:virology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D016019:Survival Analysis; D013937:Thymidine Kinase / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D000410:Alanine Transaminase; D013937:Thymidine Kinase; D014568:Urokinase-Type Plasminogen Activator; D015774:Ganciclovir
keywords: ALT; GCV; HBV; HCV; HSA; HSVtk; Hepatitis B virus; Hepatitis C virus; Human hepatocyte chimeric mouse; Human serum albumin; IFN; PegIFN-alpha; RI; RT-PCR; SCID; TK-NOG mouse; alanine aminotransferase; ganciclovir; hepatitis B virus; hepatitis C virus; herpes simplex virus type-1 thymidine kinase; human serum albumin; interferon; pegylated interferon-alpha; repopulation index; reverse transcript-polymerase chain reaction; severe combined immunodeficiency; uPA; uPA–SCID mouse; urokinase-type plasminogen activator