Efficient acute and chronic infection of stem cell-derived hepatocytes by hepatitis C virus.
dc.contributor.author | Carpentier, Arnaud | |
dc.contributor.author | Sheldon, Julie | |
dc.contributor.author | Vondran, Florian W R | |
dc.contributor.author | Brown, Richard Jp | |
dc.contributor.author | Pietschmann, Thomas | |
dc.date.accessioned | 2020-04-15T11:07:28Z | |
dc.date.available | 2020-04-15T11:07:28Z | |
dc.date.issued | 2020-02-29 | |
dc.identifier.citation | Gut. 2020 Feb 29. pii: gutjnl-2019-319354. doi: 10.1136/gutjnl-2019-319354. | en_US |
dc.identifier.pmid | 32114504 | |
dc.identifier.doi | 10.1136/gutjnl-2019-319354 | |
dc.identifier.uri | http://hdl.handle.net/10033/622231 | |
dc.description.abstract | Transcriptional 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.iso | en | en_US |
dc.publisher | BMJ Publishing Group | en_US |
dc.rights | Attribution-NonCommercial-ShareAlike 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | HCV | en_US |
dc.subject | hepatocyte | en_US |
dc.subject | immune response | en_US |
dc.subject | interferon | en_US |
dc.subject | stem cells | en_US |
dc.title | Efficient acute and chronic infection of stem cell-derived hepatocytes by hepatitis C virus. | en_US |
dc.type | Article | en_US |
dc.identifier.eissn | 1468-3288 | |
dc.contributor.department | TWINCORE, Zentrum für Experimentelle und Klinische Infektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany. | en_US |
dc.identifier.journal | Gut | en_US |
dc.source.journaltitle | Gut | |
dc.source.country | England |