title: Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection.
abstract: In order to understand the life cycle of hepatitis B virus (HBV) and to develop efficient anti-HBV drugs, a useful in vitro cell culture system which allows HBV infection and recapitulates virus-host interactions is essential; however, pre-existing in vitro HBV infection models are often problematic. Here, we examined the potential of human induced-pluripotent stem (iPS) cell-derived hepatocyte-like cells (iPS-HLCs) as an in vitro HBV infection model. Expression levels of several genes involved in HBV infection, including the sodium taurocholate cotransporting polypeptide (NTCP) gene, were gradually elevated as the differentiation status of human iPS cells proceeded to iPS-HLCs. The mRNA levels of these genes were comparable between primary human hepatocytes (PHHs) and iPS-HLCs. Following inoculation with HBV, we found significant production of HBV proteins and viral RNAs in iPS-HLCs. The three major forms of the HBV genome were detected in iPS-HLCs by Southern blotting analysis. Anti-HBV agents entecavir and Myrcludex-B, which are a nucleoside analogue reverse transcriptase inhibitor and a synthetic pre-S1 peptide, respectively, significantly inhibited HBV infection in iPS-HLCs. These data demonstrate that iPS-HLCs can be used as a promising in vitro HBV infection model.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.|Laboratory of Regulatory Sciences for Oligonucleotide Therapeutics, Clinical Drug Development Unit, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sakurai
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Mitani
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.|iPS Cell-Based Research Project on Hepatic Toxicity and Metabolism, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.|Laboratory of Hepatocyte Regulation, National Institute of Biomedical Innovation, Health and Nutrition, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tachibana
authors.affiliation: Department of Virology 2, National Institute of Infectious Diseases, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Watashi
authors.affiliation: Department of Virology 2, National Institute of Infectious Diseases, Japan.
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.affiliation: Department of Virology &Liver unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Sayuki
authors.initials: S
authors.lastname: Iijima
authors.affiliation: Department of Virology &Liver unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.|iPS Cell-Based Research Project on Hepatic Toxicity and Metabolism, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.|Laboratory of Hepatocyte Regulation, National Institute of Biomedical Innovation, Health and Nutrition, Japan.|Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.|Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029363:Organic Anion Transporters, Sodium-Dependent; D012367:RNA, Viral; D027981:Symporters; D014764:Viral Proteins; C071908:sodium-bile acid cotransporter