Evidence map›Paper›PMID 25734487›Full record

ArticleJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research2015

The Mechanism of Interferon Refractoriness During Hepatitis C Virus Infection and Its Reversal with a Peroxisome Proliferator-Activated Receptor α Agonist.

Scott A Read, Enoch S Tay, Mahsa Shahidi, John McLauchlan, Jacob George, Mark W Douglas

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

9 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
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  8. TAM receptor tyrosine kinase function and the immunopathology of liver disease.American journal of physiology. Gastrointestinal and liver physiology · 2016
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Scott A Read1 Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital , Westmead, Australia .
Enoch S Tay1 Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital , Westmead, Australia .
Mahsa Shahidi1 Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital , Westmead, Australia .
John McLauchlan2 MRC-University of Glasgow Centre for Virus Research , Glasgow, United Kingdom .
Jacob George1 Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital , Westmead, Australia .
Mark W Douglas1 Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital , Westmead, Australia .
The University of Sydney · AUMRC University of Glasgow Centre for Virus Research · GB

Funding

Medical Research Council MC_UU_12014/1
6 · The paper itself

Abstract

Patients who respond poorly to therapies for hepatitis C virus (HCV) infection display a characteristic phenotype with high basal hepatic interferon-stimulated gene (ISG) expression, but limited induction following interferon (IFN) treatment. The molecular pathways that mediate this refractory state are not known. We examined whether the AMPK activator metformin, the PPARγ agonist pioglitazone, or the PPARα agonist WY-14643 could potentiate IFN responses, reverse IFN refractoriness, and enhance viral eradication in hepatocytes. WY-14643 demonstrated the strongest antiviral synergy with IFN-α and so was tested in the context of chronic IFN activation. Cells rendered refractory to IFN by IFN-α pretreatment were resensitized by WY-14643, as demonstrated by improved STAT1 phosphorylation, promoter activation, and ISG expression. WY-14643 treatment reduced the expression of key negative regulators of IFN signaling: the AXL receptor tyrosine kinase, suppressor of cytokine signaling (SOCS) 1 and 3, which are upregulated in the IFN-refractory state. AXL is a novel regulator of IFN-α signaling that is induced by HCV infection in vitro and which may drive SOCS3 expression. Our data suggests that PPARα agonists could be a useful adjunct treatment for chronic HCV infection by reducing the expression of AXL/SOCS and increasing the sensitivity to IFN.

Indexed as

Host-Pathogen InteractionsAMP-Activated Protein KinasesAxl Receptor Tyrosine KinaseCell Line, TumorDrug Resistance, ViralGene Expression RegulationGenes, ReporterHepacivirusHepatocytesHumansInterferon-alphaLuciferasesMetforminPioglitazonePPAR alphaPPAR gammaAMP-Activated Protein KinasesAxl Receptor Tyrosine KinaseInterferon-alphaLuciferasesMetforminPioglitazonepirinixic acidPPAR alphaPPAR gammaProto-Oncogene ProteinsPyrimidinesReceptor Protein-Tyrosine KinasesRecombinant Fusion ProteinsSOCS1 protein, humanSOCS3 protein, humanSTAT1 protein, humanSTAT1 Transcription FactorSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsThiazolidinediones

Identifiers

PMID25734487
PMCPMC4490708
OpenAlexW1982830211

What OpenQuestion holds

Textmetadata
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.