ArticlePLoS biology2018
A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 111 citations in OpenAlex.
- Identification of fidelity-determined residues of Porcine reproductive and respiratory syndrome virus through structural alignment.Virulence · 2026Article
- Slow PPThe Journal of biological chemistry · 2026Article
- Evolution of the rate, molecular spectrum, and fitness effects of mutation under minimal selection in Caenorhabditis elegans.Genetics · 2026Article
- Evolution of the rate, molecular spectrum, and fitness effects of mutation under minimal selection inbioRxiv : the preprint server for biology · 2026Article
- Mutation rate variability in viral populations: Implications for lethal mutagenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mutation in enterovirus 71 nonstructural protein 3A increases genome replication fidelity and exhibits attenuated virulence in mice.Journal of virology · 2025Article
- Antimutator and Mutational Spectrum Effects Can Combine to Reduce Evolutionary Potential in Escherichia coli ΔnudJ.Molecular biology and evolution · 2025Article
- Strategies and efforts in circumventing the emergence of antiviral resistance against conventional antivirals.npj antimicrobials and resistance · 2025Review
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- Biomathematical enzyme kinetics model of prebiotic autocatalytic RNA networks: degenerating parasite-specific hyperparasite catalysts confer parasite resistance and herald the birth of molecular immunity.PLoS computational biology · 2025Article
- Embracing Complexity: What Novel Sequencing Methods Are Teaching Us About Herpesvirus Genomic Diversity.Annual review of virology · 2024Review
- The Evolutionary Interplay of Somatic and Germline Mutation Rates.Annual review of biomedical data science · 2024Review
- Mapping mutational fitness effects across the coxsackievirus B3 proteome reveals distinct profiles of mutation tolerability.PLoS biology · 2024Article
- Targeted accurate RNA consensus sequencing (tARC-seq) reveals mechanisms of replication error affecting SARS-CoV-2 divergence.Nature microbiology · 2024Article
- Cryptic proteins translated from deletion-containing viral genomes dramatically expand the influenza virus proteome.Nucleic acids research · 2024Article
- Cryptic proteins translated from deletion-containing viral genomes dramatically expand the influenza virus proteome.bioRxiv : the preprint server for biology · 2024Article
- Attenuation of neurovirulence of chikungunya virus by a single amino acid mutation in viral E2 envelope protein.Journal of biomedical science · 2024Article
- Open questions in the social lives of viruses.Journal of evolutionary biology · 2023Review
- Article
- Kill or corrupt: Mechanisms of action and drug-resistance of nucleotide analogues against SARS-CoV-2.Antiviral research · 2023Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Mutation rates can evolve through genetic drift, indirect selection due to genetic hitchhiking, or direct selection on the physicochemical cost of high fidelity. However, for many systems, it has been difficult to disentangle the relative impact of these forces empirically. In RNA viruses, an observed correlation between mutation rate and virulence has led many to argue that their extremely high mutation rates are advantageous because they may allow for increased adaptability. This argument has profound implications because it suggests that pathogenesis in many viral infections depends on rare or de novo mutations. Here, we present data for an alternative model whereby RNA viruses evolve high mutation rates as a byproduct of selection for increased replicative speed. We find that a poliovirus antimutator, 3DG64S, has a significant replication defect and that wild-type (WT) and 3DG64S populations have similar adaptability in 2 distinct cellular environments. Experimental evolution of 3DG64S under selection for replicative speed led to reversion and compensation of the fidelity phenotype. Mice infected with 3DG64S exhibited delayed morbidity at doses well above the lethal level, consistent with attenuation by slower growth as opposed to reduced mutational supply. Furthermore, compensation of the 3DG64S growth defect restored virulence, while compensation of the fidelity phenotype did not. Our data are consistent with the kinetic proofreading model for biosynthetic reactions and suggest that speed is more important than accuracy. In contrast with what has been suggested for many RNA viruses, we find that within-host spread is associated with viral replicative speed and not standing genetic diversity.
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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.