ArticlePloS one2013
Interferon and ribavirin combination treatment synergistically inhibit HCV internal ribosome entry site mediated translation at the level of polyribosome formation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 14 papers.
What it found
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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.
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.
Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
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- Discovery of Synergistic and Antagonistic Drug Combinations against SARS-CoV-2 In Vitro.bioRxiv : the preprint server for biology · 2020Article
- Exacerbated Apoptosis of Cells Infected with Infectious Bursal Disease Virus upon Exposure to Interferon Alpha.Journal of virology · 2018Article
- Antiviral Effect of Ribavirin against HCV Associated with Increased Frequency of G-to-A and C-to-U Transitions in Infectious Cell Culture Model.Scientific reports · 2018Article
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- Staufen1 promotes HCV replication by inhibiting protein kinase R and transporting viral RNA to the site of translation and replication in the cells.Nucleic acids research · 2016Article
- Hepatitis C Virus Infection Induces Autophagy as a Prosurvival Mechanism to Alleviate Hepatic ER-Stress Response.Viruses · 2016Review
- Cellular Mechanism for Impaired Hepatitis C Virus Clearance by Interferon Associated with IFNL3 Gene Polymorphisms Relates to Intrahepatic Interferon-λ Expression.The American journal of pathology · 2016Article
- Evaluation of antiviral drug synergy in an infectious HCV system.Antiviral therapy · 2016Article
- Persistent hepatitis C virus infection impairs ribavirin antiviral activity through clathrin-mediated trafficking of equilibrative nucleoside transporter 1.Journal of virology · 2015Article
- Article
Corrections and comments
- Retraction · 2024-08-05Concerns/Issues about Image · Duplication of/in Image · Euphemisms for Duplication · Investigation by Journal/Publisher · Investigation by Third Party · Objections by Author(s) · Original Data and/or Images not Provided and/or not Available · Unreliable Results and/or Conclusions · Upgrade/Update of Prior Notice(s) · · see also: https://pubpeer.com/publications/112FC0346AD5C1FA38660AFF6CE4EC
- Expression of concern · 2022-03-31Cites Retracted Work · Concerns/Issues about Data · Concerns/Issues about Image · Upgrade/Update of Prior Notice(s) · · see also: https://pubpeer.com/publications/112FC0346AD5C1FA38660AFF6CE4EC
- Expression of concern
- Retracted
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
purposeAlthough chronic hepatitis C virus (HCV) infection has been treated with the combination of interferon alpha (IFN-α) and ribavirin (RBV) for over a decade, the mechanism of antiviral synergy is not well understood. We aimed to determine the synergistic antiviral mechanisms of IFN-α and RBV combination treatment using HCV cell culture.
methodsThe antiviral efficacy of IFN-α, RBV alone and in combination was quantitatively measured using HCV infected and replicon cell culture. Direct antiviral activity of these two drugs at the level of HCV internal ribosome entry site (IRES) mediated translation in Huh-7 cell culture was investigated. The synergistic antiviral effect of IFN-α and RBV combination treatment was verified using both the CalcuSyn Software and MacSynergy Software.
resultsRBV combination with IFN-α efficiently inhibits HCV replication cell culture. Our results demonstrate that IFN-α, interferon lambda (IFN-λ) and RBV each inhibit the expression of HCV IRES-GFP and that they have a minimal effect on the expression of GFP in which the translation is not IRES dependent. The combination treatments of RBV along with IFN-α or IFN-λ were highly synergistic with combination indexes <1. We show that IFN-α treatment induce levels of PKR and eIF2α phosphorylation that prevented ribosome loading of the HCV IRES-GFP mRNA. Silencing of PKR expression in Huh-7 cells prevented the inhibitory effect of IFN-α on HCV IRES-GFP expression. RBV also blocked polyribosome loading of HCV-IRES mRNA through the inhibition of cellular IMPDH activity, and induced PKR and eIF2α phosphorylation. Knockdown of PKR or IMPDH prevented RBV induced HCV IRES-GFP translation.
conclusionsWe demonstrated both IFN-α and RBV inhibit HCV IRES through prevention of polyribosome formation. The combination of IFN-α and RBV treatment synergistically inhibits HCV IRES translation via using two different mechanisms involving PKR activation and depletion of intracellular guanosine pool through inhibition of IMPDH.
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What OpenQuestion holds
Registered trials
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.