title: Modulating innate immunity improves hepatitis C virus infection and replication in stem cell-derived hepatocytes.
abstract: In this study, human embryonic stem cell-derived hepatocytes (hESC-Heps) were investigated for their ability to support hepatitis C virus (HCV) infection and replication. hESC-Heps were capable of supporting the full viral life cycle, including the release of infectious virions. Although supportive, hESC-Hep viral infection levels were not as great as those observed in Huh7 cells. We reasoned that innate immune responses in hESC-Heps may lead to the low level of infection and replication. Upon further investigation, we identified a strong type III interferon response in hESC-Heps that was triggered by HCV. Interestingly, specific inhibition of the JAK/STAT signaling pathway led to an increase in HCV infection and replication in hESC-Heps. Of note, the interferon response was not evident in Huh7 cells. In summary, we have established a robust cell-based system that allows the in-depth study of virus-host interactions in vitro.
authors: Shantou University Medical College, Shantou 515041, People's Republic of China ; MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK ; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G11 5JR, UK.
authors: Xiaoling
authors: X
authors: Zhou
authors: Shantou University Medical College, Shantou 515041, People's Republic of China ; MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK ; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G11 5JR, UK.
authors: Pingnan
authors: P
authors: Sun
authors: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors: Baltasar
authors: B
authors: Lucendo-Villarin
authors: MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G11 5JR, UK.
authors: Allan G N
authors: AG
authors: Angus
authors: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors: Dagmara
authors: D
authors: Szkolnicka
authors: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors: Kate
authors: K
authors: Cameron
authors: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors: Sarah L
authors: SL
authors: Farnworth
authors: MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G11 5JR, UK.
authors: Arvind H
authors: AH
authors: Patel
authors: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors: David C
authors: DC
authors: Hay
mesh_terms: D002460:Cell Line; D016174:Hepacivirus / Q000276:immunology / Q000472:pathogenicity*; D006526:Hepatitis C / Q000276:immunology; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D013234:Stem Cells / Q000821:virology*; D014779:Virus Replication / Q000502:physiology