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Efficient acute and chronic infection of stem cell-derived hepatocytes by hepatitis C virus.
Carpentier, Arnaud Sheldon, Julie Vondran, Florian W R Brown, Richard Jp Pietschmann, Thomas
Carpentier, Arnaud
Sheldon, Julie
Vondran, Florian W R
Brown, Richard Jp
Pietschmann, Thomas
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2020-02-29
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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.
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Gut. 2020 Feb 29. pii: gutjnl-2019-319354. doi: 10.1136/gutjnl-2019-319354.
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en
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1468-3288
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Attribution-NonCommercial-ShareAlike 4.0 International