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Use of human hepatocyte-like cells derived from induced pluripotent stem cells as a model for hepatocytes in hepatitis C virus infection

Yoshida, Takeshi, Takayama, Kazuo, Kondoh, Masuo, Sakurai, Fuminori, Tani, Hideki, Sakamoto, Naoya, Matsuura, Yoshiharu, Mizuguchi, Hiroyuki, Yagi, Kiyohito
Biochemical and biophysical research communications 2011 v.416 no.1-2 pp. 119-124
Hepatitis C virus, Pan troglodytes, RNA, adverse effects, antibodies, biological resistance, drugs, genome, hepatocytes, humans, induced pluripotent stem cells, interferons, models, occludins, receptors, viruses
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.