ArticlePLoS pathogens2010
A multi-step process of viral adaptation to a mutagenic nucleoside analogue by modulation of transition types leads to extinction-escape.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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64 citing papers in PubMed, 95 citations in OpenAlex.
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- Antiviral Efficacy of Lignan Derivatives (-)-Asarinin and Sesamin Against Foot-and-Mouth Disease Virus by Targeting RNA-Dependent RNA Polymerase (3DVeterinary sciences · 2025Article
- Isolation, characterization, and biological evaluation of endophytic fungi fromFrontiers in molecular biosciences · 2025Article
- Alterations of SARS-CoV-2 Evolutionary Dynamics by Pharmaceutical Factors.Infectious diseases & immunity · 2024Review
- Fitness-Dependent, Mild Mutagenic Activity of Sofosbuvir for Hepatitis C Virus.Antimicrobial agents and chemotherapy · 2023Article
- Directed Evolution of Seneca Valley Virus in Tumorsphere and Monolayer Cell Cultures of a Small-Cell Lung Cancer Model.Cancers · 2023Article
- Quasispecies Nature of RNA Viruses: Lessons from the Past.Vaccines · 2023Review
- Atypical Mutational Spectrum of SARS-CoV-2 Replicating in the Presence of Ribavirin.Antimicrobial agents and chemotherapy · 2023Article
- Non-Nucleoside Inhibitors Decrease Foot-and-Mouth Disease Virus Replication by Blocking the Viral 3DViruses · 2022Article
- Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity.Viruses · 2022Review
- Enteroviral Infections in the First Three Months of Life.Pathogens (Basel, Switzerland) · 2022Review
- Guanosine inhibits hepatitis C virus replication and increases indel frequencies, associated with altered intracellular nucleotide pools.PLoS pathogens · 2022Article
- Viruses in astrobiology.Frontiers in microbiology · 2022Review
- A Novel Plasmid DNA-Based Foot and Mouth Disease Virus Minigenome for Intracytoplasmic mRNA Production.Viruses · 2021Article
- Inhibition of viral RNA-dependent RNA polymerases with clinically relevant nucleotide analogs.The Enzymes · 2021Article
- Rescuing eGFP-Tagged Canine Distemper Virus for 40 Serial Passages Separately in Ribavirin- and Non-Treated Cells: Comparative Analysis of Viral Mutation Profiles.Frontiers in cellular and infection microbiology · 2021Article
- Residues within the Foot-and-Mouth Disease Virus 3DJournal of virology · 2020Article
- Lethal Mutagenesis of Rift Valley Fever Virus Induced by Favipiravir.Antimicrobial agents and chemotherapy · 2019Article
- Contribution of a Multifunctional Polymerase Region of Foot-and-Mouth Disease Virus to Lethal Mutagenesis.Journal of virology · 2018Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance of viruses to mutagenic agents is an important problem for the development of lethal mutagenesis as an antiviral strategy. Previous studies with RNA viruses have documented that resistance to the mutagenic nucleoside analogue ribavirin (1-β-D-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide) is mediated by amino acid substitutions in the viral polymerase that either increase the general template copying fidelity of the enzyme or decrease the incorporation of ribavirin into RNA. Here we describe experiments that show that replication of the important picornavirus pathogen foot-and-mouth disease virus (FMDV) in the presence of increasing concentrations of ribavirin results in the sequential incorporation of three amino acid substitutions (M296I, P44S and P169S) in the viral polymerase (3D). The main biological effect of these substitutions is to attenuate the consequences of the mutagenic activity of ribavirin -by avoiding the biased repertoire of transition mutations produced by this purine analogue-and to maintain the replicative fitness of the virus which is able to escape extinction by ribavirin. This is achieved through alteration of the pairing behavior of ribavirin-triphosphate (RTP), as evidenced by in vitro polymerization assays with purified mutant 3Ds. Comparison of the three-dimensional structure of wild type and mutant polymerases suggests that the amino acid substitutions alter the position of the template RNA in the entry channel of the enzyme, thereby affecting nucleotide recognition. The results provide evidence of a new mechanism of resistance to a mutagenic nucleoside analogue which allows the virus to maintain a balance among mutation types introduced into progeny genomes during replication under strong mutagenic pressure.
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