Evidence map›Paper›PMID 32114504›Full record

ArticleGut2020

Efficient acute and chronic infection of stem cell-derived hepatocytes by hepatitis C virus.

Arnaud Carpentier, Julie Sheldon, Florian W R Vondran, Richard Jp Brown, Thomas Pietschmann

Open access · hybridAbstract read
In one paragraph

Article in Gut, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 26 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Arnaud CarpentierInstitute of Experimental Virology, Twincore, Hannover, Germany arnaud.carpentier@twincore.de thomas.pietschmann@twincore.de.ORCID 0000-0002-6994-4689
Julie SheldonInstitute of Experimental Virology, Twincore, Hannover, Germany.
Florian W R VondranReMediES, Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany.
Richard Jp BrownInstitute of Experimental Virology, Twincore, Hannover, Germany.
Thomas PietschmannInstitute of Experimental Virology, Twincore, Hannover, Germany arnaud.carpentier@twincore.de thomas.pietschmann@twincore.de.
Medizinische Hochschule Hannover · DECenter for Experimental and Clinical Infection Research · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

OBJECTIVE AND

designHuman stem cell-derived hepatocyte-like cells (HLCs) have shown high potential as authentic model for dissection of the HCV life cycle and virus-induced pathogenesis. However, modest HCV replication, possibly due to robust innate immune responses, limits their broader use. To overcome these limitations and to dissect the mechanisms responsible for control of HCV, we analysed expression of key components of the interferon (IFN) system in HLCs, assessed permissiveness for different HCV strains and blocked innate immune signalling by pharmacological intervention.

resultsTranscriptional 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 1×10

conclusionThis authentic human cell model is well suited to examine acute and chronic host-HCV interactions, particularly IFN-triggered antiviral effector functions and mechanisms of innate immune control of HCV infection.

Indexed as

DEAD Box Protein 58Enzyme InhibitorsHepacivirusHepatocytesHost-Pathogen InteractionsHumansImmune EvasionImmunity, InnateInterferon-Induced Helicase, IFIH1InterferonsJanus KinasesModels, ImmunologicalNitrilesPyrazolesPyrimidinesReceptors, ImmunologicDEAD Box Protein 58Enzyme InhibitorsIFIH1 protein, humanInterferon-Induced Helicase, IFIH1InterferonsJanus KinasesNitrilesPyrazolesPyrimidinesReceptors, ImmunologicRIGI protein, humanruxolitinibHCVhepatocyteimmune responseinterferonstem cells

Identifiers

PMID32114504
PMCPMC7456736
OpenAlexW3007924411

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.