title: Use of human hepatocyte-like cells derived from induced pluripotent stem cells as a model for hepatocytes in hepatitis C virus infection.
abstract: Host tropism of hepatitis C virus (HCV) is limited to human and chimpanzee. HCV infection has never been fully understood because there are few conventional models for HCV infection. Human induced pluripotent stem cell-derived hepatocyte-like (iPS-Hep) cells have been expected to use for drug discovery to predict therapeutic activities and side effects of compounds during the drug discovery process. However, the suitability of iPS-Hep cells as an experimental model for HCV research is not known. Here, we investigated the entry and genomic replication of HCV in iPS-Hep cells by using HCV pseudotype virus (HCVpv) and HCV subgenomic replicons, respectively. We showed that iPS-Hep cells, but not iPS cells, were susceptible to infection with HCVpv. The iPS-Hep cells expressed HCV receptors, including CD81, scavenger receptor class B type I (SR-BI), claudin-1, and occludin; in contrast, the iPS cells showed no expression of SR-BI or claudin-1. HCV RNA genome replication occurred in the iPS-Hep cells. Anti-CD81 antibody, an inhibitor of HCV entry, and interferon, an inhibitor of HCV genomic replication, dose-dependently attenuated HCVpv entry and HCV subgenomic replication in iPS-Hep cells, respectively. These findings suggest that iPS-Hep cells are an appropriate model for HCV infection.
authors.affiliation: Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takayama
authors.forename: Masuo
authors.initials: M
authors.lastname: Kondoh
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sakurai
authors.forename: Hideki
authors.initials: H
authors.lastname: Tani
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Yagi
mesh_terms: D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D008954:Models, Biological; D039904:Pluripotent Stem Cells / Q000166:cytology; D053586:Virus Internalization; D014779:Virus Replication