Hepatitis C Virus

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Description This new culture system creates stem cell-derived human hepatocyte-like cells which are Hepatitis C Virus (HCV) infectable. This FSU-created technology establishes a new noncancerous and renewable cell culture system for HCV infection; enables direct infection by patient sera in vitro; identifies a defined transition to HCV permissiveness during hepatocyte differentiation; and demonstrates the feasibility of generating viral-resistant human hepatocyte-like cells in vitro. Primary human hepatocytes (PHHs) isolated from patient biopsies represent the most physiologically relevant cell culture model for hepatitis C virus (HCV) infection. However, these primary cells are not readily accessible, display individual variability, and are largely refractory to genetic manipulation. The  hepatocyte-like cells derived from stem cells not only overcomes these shortcomings but can also provide an unlimited source of non-cancer cells for both research and cell therapy. The system reports a novel infection model based upon differentiated human hepatocyte-like cells (DHHs) derived from stem cells, including human embryonic (hESCs) and induced pluripotent stem cells (iPSCs). Differentiated human hepatocyte-like cells (DHHs) derived from pluripotent stem cells have demonstrated hepatic functions but have not been explored for HCV infection studies as here. The ability to directly infect cultured cells with HCV patient serum, to study defined stages of viral permissiveness, and to produce genetically modified cells with desired phenotypes all have broad significance for host-pathogen interactions, drug resistance analysis and drug therapy.