Modulating innate immunity improves Hepatitis C virus infection and replication in stem cell-derived hepatocytes

Zhou, X., Sun, P., Lucendo-Villarin, B., Angus, A. G.N., Szkolnicka, D., Cameron, K., Farnworth, S. L., Patel, A. H. and Hay, D. C. (2014) Modulating innate immunity improves Hepatitis C virus infection and replication in stem cell-derived hepatocytes. Stem Cell Reports, 3(1), pp. 204-214. (doi:10.1016/j.stemcr.2014.04.018) (PMID:25068132) (PMCID:PMC4110790)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Angus, Dr Allan and Patel, Professor Arvind and Zhou, Dr Xiaoling
Authors: Zhou, X., Sun, P., Lucendo-Villarin, B., Angus, A. G.N., Szkolnicka, D., Cameron, K., Farnworth, S. L., Patel, A. H., and Hay, D. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Stem Cell Reports
Publisher:Elsevier Inc.
ISSN:2213-6711
ISSN (Online):2213-6711
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Stem Cell Reports 3(1):204-214
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
633481Development of Novel in Vitro Models for Hepatitus B virus and Hepatitus C virus Infection and ReplicationArvind PatelMedical Research Council (MRC)MR/K008757/1III - CENTRE FOR VIRUS RESEARCH
656491Basis of the host range and tissue tropism for hepatitis C virusArvind PatelMedical Research Council (MRC)MC_UU_12014/2MVLS III - CENTRE FOR VIRUS RESEARCH