Human iPS‐derived hepatocyte‐like cells as a model for hepatitis C virus infection

Abstract

Approximately 130–200 million people are estimated to be infected with hepatitis C virus (HCV) worldwide, and over 350 thousand people die from HCV‐related disease every year worldwide. Therefore, overcoming HCV is a critical issue for the World Health Organization. The host tropism of HCV is limited to human and chimpanzee, and a convenient model for HCV infection has never been fully developed. The establishment of human induced pluripotent stem (iPS) cell technology has led to innovative iPS‐based models for drug discovery. Protocols for preparation of iPS‐derived hepatocyte‐like cells (iPS‐Hep) have been developed; however, the suitability of iPS‐Hep cells as a model for HCV infection remains unclear. In the present study, we investigated infection of HCV pseudotype virus (HCVpv) and replication of the HCV subgenome in iPS‐Hep cells. We demonstrated that HCVpv infected iPS‐Hep cells but not iPS cells, and the HCV subgenome replicated in iPS‐Hep cells but not in iPS cells. Inhibitors of HCV replication, interferon, and HCV entry, anti‐CD81 antibody, attenuated HCV replication within the iPS‐Hep cells, and the HCVpv entry into the iPS‐Hep cells. These findings suggest that iPS‐Hep cells are a potent model for HCV infection. As a promising new tool for HCV research, iPS‐Hep cells will facilitate our understanding of the biology of HCV and the development of anti‐HCV drugs.