Evidence map›Paper›PMID 20149251›Full record

ArticleVirology journal2010

Impaired antiviral activity of interferon alpha against hepatitis C virus 2a in Huh-7 cells with a defective Jak-Stat pathway.

Sidhartha Hazari, Partha K Chandra, Bret Poat, Sibnarayan Datta, Robert F Garry, Timothy P Foster, Gus Kousoulas, Takaji Wakita, Srikanta Dash

Open access · goldAbstract read
In one paragraph

Article in Virology journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

21 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Role of STAT1 in the resistance of HBV to IFN-α.Experimental and therapeutic medicine · 2021
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  10. Retracted: Inhibition of hepatitis C virus replication by intracellular delivery of multiple siRNAs by nanosomes.Molecular therapy : the journal of the American Society of Gene Therapy · 2012
    Article
  11. Article
  12. Article
  13. Stability of lyophilized siRNA nanosome formulations.International journal of pharmaceutics · 2012
    Article
  14. Development and optimization of nanosomal formulations for siRNA delivery to the liver.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2012
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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

9 authors at 3 institutions in 2 countries.

Sidhartha HazariDepartment of Pathology and Laboratory Medicine, Tulane University of Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112, USA.
Partha K Chandra
Bret Poat
Sibnarayan Datta
Robert F Garry
Timothy P Foster
Gus Kousoulas
Takaji Wakita
Srikanta Dash
Tulane University · USLouisiana State University · USNational Institute of Infectious Diseases · JP

Funding

GENETICS &FUNCTIONS OF HSV1 GK IN VIRUS ENTRY &EGRESSR01AI043000 · NIAID · LOUISIANA STATE UNIV A&M COL BATON ROUGE · PI KOUSOULAS, KONSTANTIN G · 1999 to 2009
$2.4M
Hepatocarcinogenesis Secondary to Hepatitis CR01CA127481 · NCI · TULANE UNIVERSITY OF LOUISIANA · PI DASH, SRIKANTA · 2008 to 2012
$1.4M
HIV-1 Tat modulation of HCV replication and pathogenesisR21DK070551 · NIDDK · TULANE UNIVERSITY OF LOUISIANA · PI GARRY, ROBERT F · 2005 to 2006
$440k
Intracellular immunization strategy in inhibit HCV related liver cancerR21CA129776 · NCI · TULANE UNIVERSITY OF LOUISIANA · PI DASH, SRIKANTA · 2009 to 2010
$343k
NCI NIH HHS CA127481NCI NIH HHS CA129776NIAID NIH HHS AI43000NIDDK NIH HHS DK070551
6 · The paper itself

Abstract

backgroundThe sustained virological response to interferon-alpha (IFN-alpha) in individuals infected with hepatitis C virus (HCV) genotype 1 is only 50%, but is about 80% in patients infected with genotype 2-6 viruses. The molecular mechanisms explaining the differences in IFN-alpha responsiveness between HCV 1 and other genotypes have not been elucidated.

resultsVirus and host cellular factors contributing to IFN responsiveness were analyzed using a green fluorescence protein (GFP) based replication system of HCV 2a and Huh-7 cell clones that either possesses or lack a functional Jak-Stat pathway. The GFP gene was inserted into the C-terminal non-structural protein 5A of HCV 2a full-length and sub-genomic clones. Both HCV clones replicated to a high level in Huh-7 cells and could be visualized by either fluorescence microscopy or flow cytometric analysis. Huh-7 cells transfected with the GFP tagged HCV 2a genome produced infectious virus particles and the replication of fluorescence virus particles was demonstrated in naïve Huh-7.5 cells after infection. IFN-alpha effectively inhibited the replication of full-length as well as sub-genomic HCV 2a clones in Huh-7 cells with a functional Jak-Stat pathway. However, the antiviral effect of IFN-alpha against HCV 2a virus was not observed in Huh-7 cell clones with a defect in Jak-Stat signaling. HCV infection or replication did not alter IFN-alpha induced Stat phosphorylation or ISRE promoter-luciferase activity in both the sensitive and resistant Huh-7 cell clones.

conclusionsThe cellular Jak-Stat pathway is critical for a successful IFN-alpha antiviral response against HCV 2a. HCV infection or replication did not alter signaling by the Jak-Stat pathway. GFP labeled JFH1 2a replicon based stable cell lines with IFN sensitive and IFN resistant phenotypes can be used to develop new strategies to overcome IFN-resistance against hepatitis C.

Indexed as

Cell LineGenes, ReporterGenotypeGreen Fluorescent ProteinsHepacivirusHepatocytesHumansInterferon-alphaJanus KinasesRecombinant Fusion ProteinsRNA-Dependent RNA PolymeraseStaining and LabelingSTAT Transcription FactorsViral Nonstructural ProteinsGreen Fluorescent ProteinsInterferon-alphaJanus KinasesNS-5 protein, hepatitis C virusRecombinant Fusion ProteinsRNA-Dependent RNA PolymeraseSTAT Transcription FactorsViral Nonstructural Proteins

Identifiers

PMID20149251
PMCPMC2831880
OpenAlexW2077970270

What OpenQuestion holds

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LicenceCC BY
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.