ArticleJournal of virology2007
Lethal mutagenesis of poliovirus mediated by a mutagenic pyrimidine analogue.
Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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.
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
27 citing papers in PubMed, 48 citations in OpenAlex.
- Mutation of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461.PloS one · 2011Trial
- The multiple roles of viral 3DVirulence · 2024Review
- Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity.Viruses · 2022Review
- Distinct dual antiviral mechanism that enhances hepatitis B virus mutagenesis and reduces viral DNA synthesis.Antiviral research · 2019Article
- Arenavirus Quasispecies and Their Biological Implications.Current topics in microbiology and immunology · 2016Review
- Extinction of hepatitis C virus by ribavirin in hepatoma cells involves lethal mutagenesis.PloS one · 2013Article
- Anti-HIV-1 activity of resveratrol derivatives and synergistic inhibition of HIV-1 by the combination of resveratrol and decitabine.Bioorganic & medicinal chemistry letters · 2012Article
- Nucleoside analogue mutagenesis of a single-stranded DNA virus: evolution and resistance.Journal of virology · 2012Article
- Viral quasispecies evolution.Microbiology and molecular biology reviews : MMBR · 2012Review
- Activity of a novel combined antiretroviral therapy of gemcitabine and decitabine in a mouse model for HIV-1.Antimicrobial agents and chemotherapy · 2012Article
- Mutational robustness of an RNA virus influences sensitivity to lethal mutagenesis.Journal of virology · 2012Article
- What is the role of motif D in the nucleotide incorporation catalyzed by the RNA-dependent RNA polymerase from poliovirus?PLoS computational biology · 2012Article
- Sensitivity of mitochondrial transcription and resistance of RNA polymerase II dependent nuclear transcription to antiviral ribonucleosides.PLoS pathogens · 2012Article
- Mutation induced extinction in finite populations: lethal mutagenesis and lethal isolation.PLoS computational biology · 2012Article
- Fidelity variants of RNA dependent RNA polymerases uncover an indirect, mutagenic activity of amiloride compounds.PLoS pathogens · 2010Article
- Viral mutation rates.Journal of virology · 2010Review
- Does mutational robustness inhibit extinction by lethal mutagenesis in viral populations?PLoS computational biology · 2010Article
- Article
- Potential benefits of sequential inhibitor-mutagen treatments of RNA virus infections.PLoS pathogens · 2009Article
- 5-Azacytidine can induce lethal mutagenesis in human immunodeficiency virus type 1.Journal of virology · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Lethal mutagenesis is the mechanism of action of ribavirin against poliovirus (PV) and numerous other RNA viruses. However, there is still considerable debate regarding the mechanism of action of ribavirin against a variety of RNA viruses. Here we show by using T7 RNA polymerase-mediated production of PV genomic RNA, PV polymerase-catalyzed primer extension, and cell-free PV synthesis that a pyrimidine ribonucleoside triphosphate analogue (rPTP) with ambiguous base-pairing capacity is an efficient mutagen of the PV genome. The in vitro incorporation properties of rPTP are superior to ribavirin triphosphate. We observed a log-linear relationship between virus titer reduction and the number of rPMP molecules incorporated. A PV genome encoding a high-fidelity polymerase was more sensitive to rPMP incorporation, consistent with diminished mutational robustness of high-fidelity PV. The nucleoside (rP) did not exhibit antiviral activity in cell culture, owing to the inability of rP to be converted to rPMP by cellular nucleotide kinases. rP was also a poor substrate for herpes simplex virus thymidine kinase. The block to nucleoside phosphorylation could be bypassed by treatment with the P nucleobase, which exhibited both antiviral activity and mutagenesis, presumably a reflection of rP nucleotide formation by a nucleotide salvage pathway. These studies provide additional support for lethal mutagenesis as an antiviral strategy, suggest that rPMP prodrugs may be highly efficacious antiviral agents, and provide a new tool to determine the sensitivity of RNA virus genomes to mutagenesis as well as interrogation of the impact of mutational load on the population dynamics of these viruses.
Indexed as
Identifiers
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.