Title: Human pluripotent stem cell derived hepatocytes support complete replication of hepatitis C virus
Authors: Roelandt, Philip ×
Obeid, Susan
Paeshuyse, Jan
Vanhove, Jolien
Van Lommel, Alfons
Nahmias, Yaakov
Nevens, Frederik
Neyts, Johan
Verfaillie, Catherine #
Issue Date: Aug-2012
Publisher: Elsevier Science Publishers
Series Title: Journal of Hepatology vol:57 issue:2 pages:246-251
Abstract: BACKGROUND & AIMS: Worldwide about 180 million people are chronically infected with the hepatitis C virus (HCV). Current in vitro culture systems for HCV depend chiefly on human hepatoma cell lines. Although primary human hepatocytes support HCV infection in vitro, and immunodeficient mice repopulated with human hepatocytes support HCV infection in vivo, these models are limited because of shortage of human livers to isolate hepatocytes. Therefore, there is significant interest in the establishment of a HCV culture system in human stem cell-derived hepatocyte-like cells. METHODS: Human embryonic stem cell (hESC)-derived hepatocytes were infected with HCV in the presence or absence of direct acting antivirals. After inoculation, replication of HCV was analyzed extensively. RESULTS: We demonstrate that human embryonic stem cell (hESC)-derived hepatocytes can be infected with the HCV JFH1 genotype 2a, resulting in the production of viral RNA in the stem cell progeny. Viral replication is inhibited by a non-nucleoside HCV polymerase-inhibitor (HCV-796), a cyclophilin binding molecule (Debio 025-Alisporivir) and the protease inhibitor VX-950 (Telaprevir). Stem cell-derived hepatocytes produced for more than 10 days HCV core protein as well as virions that were capable of re-infecting hepatoma cells. CONCLUSIONS: Hepatocytes derived from hESC support the complete HCV replication cycle (including the production of infectious virus) and viral replication in these cells is efficiently inhibited by selective inhibitors of HCV replication.
ISSN: 0168-8278
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Department of Development and Regeneration - miscellaneous (+)
Embryo and Stemcells (-)
Translational Cell & Tissue Research
× corresponding author
# (joint) last author

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