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dc.contributor.authorCarpentier, Arnaud
dc.contributor.authorSheldon, Julie
dc.contributor.authorVondran, Florian W R
dc.contributor.authorBrown, Richard Jp
dc.contributor.authorPietschmann, Thomas
dc.date.accessioned2020-04-15T11:07:28Z
dc.date.available2020-04-15T11:07:28Z
dc.date.issued2020-02-29
dc.identifier.citationGut. 2020 Feb 29. pii: gutjnl-2019-319354. doi: 10.1136/gutjnl-2019-319354.en_US
dc.identifier.pmid32114504
dc.identifier.doi10.1136/gutjnl-2019-319354
dc.identifier.urihttp://hdl.handle.net/10033/622231
dc.description.abstractTranscriptional profiling revealed that HLCs constitutively express messenger RNA of RLRs, and members of the IFN pathway. Moreover, HLCs upregulated IFNs and canonical interferon-regulated genes (IRGs) upon transfection with the double-stranded RNA mimic poly(I:C). Infection of HLCs with Jc1-HCVcc produced only limited viral progeny. In contrast, infection with p100, a Jc1-derived virus population with enhanced replication fitness and partial resistance to IFN, resulted in robust yet transient viraemia. Viral titres declined concomitant with a peak of IRG induction. Addition of ruxolitinib, a JAK/STAT inhibitor, permitted chronic infection and raised p100 infectious virus titres to 1×105 FFU/mL. IRGs expression profiling in infected HLCs revealed a landscape of HCV-dependent transcriptional changes similar to HCV-infected primary human hepatocytes, but distinct from Huh-7.5 cells. Withdrawal of ruxolitinib restored innate immune responses and resulted in HCV clearance.en_US
dc.language.isoenen_US
dc.publisherBMJ Publishing Groupen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectHCVen_US
dc.subjecthepatocyteen_US
dc.subjectimmune responseen_US
dc.subjectinterferonen_US
dc.subjectstem cellsen_US
dc.titleEfficient acute and chronic infection of stem cell-derived hepatocytes by hepatitis C virus.en_US
dc.typeArticleen_US
dc.identifier.eissn1468-3288
dc.contributor.departmentTWINCORE, Zentrum für Experimentelle und Klinische Infektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalGuten_US
dc.source.journaltitleGut
dc.source.countryEngland


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