ArticleThe Journal of biological chemistry2014
RNA virus population diversity, an optimum for maximal fitness and virulence.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 103 citations in OpenAlex.
- Mechanism of Forced-Copy-Choice RNA Recombination by Enteroviral RNA-Dependent RNA Polymerases.ACS bio & med chem Au · 2025Article
- A novel immunoinformatic approach for design and evaluation of heptavalent multiepitope foot-and-mouth disease virus vaccine.BMC veterinary research · 2025Article
- Molecular basis of RNA recombination in the 3'UTR of chikungunya virus genome.Nucleic acids research · 2024Article
- Evolutionary Adaptation of an RNA Bacteriophage to Repeated Freezing and Thawing Cycles.International journal of molecular sciences · 2024Article
- A tradeoff between enterovirus A71 particle stability and cell entry.Nature communications · 2023Article
- High-resolution mapping reveals the mechanism and contribution of genome insertions and deletions to RNA virus evolution.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- APEX3 - An Optimized Tool for Rapid and Unbiased Proximity Labeling.Journal of molecular biology · 2023Article
- A Virus Is a Community: Diversity within Negative-Sense RNA Virus Populations.Microbiology and molecular biology reviews : MMBR · 2022Review
- Induced intra- and intermolecular template switching as a therapeutic mechanism against RNA viruses.Molecular cell · 2021Article
- The nucleotide addition cycle of the SARS-CoV-2 polymerase.Cell reports · 2021Article
- The nucleotide addition cycle of the SARS-CoV-2 polymerase.bioRxiv : the preprint server for biology · 2021Article
- Animal and human RNA viruses: genetic variability and ability to overcome vaccines.Archives of microbiology · 2021Review
- Social Networking of Quasi-Species Consortia drive Virolution via Persistence.AIMS microbiology · 2021Review
- Polymerase Fidelity Contributes to Foot-and-Mouth Disease Virus Pathogenicity and TransmissibilityJournal of virology · 2020Article
- Microfluidics in Single-Cell Virology: Technologies and Applications.Trends in biotechnology · 2020Review
- Amino Acid Substitutions Associated with Treatment Failure for Hepatitis C Virus Infection.Journal of clinical microbiology · 2020Article
- Genotypes diversity of env gene of Bovine leukemia virus in Western Siberia.BMC genetics · 2020Article
- Residues within the Foot-and-Mouth Disease Virus 3DJournal of virology · 2020Article
- They are what you eat: Shaping of viral populations through nutrition and consequences for virulence.PLoS pathogens · 2020Review
- Picornaviral polymerase domain exchanges reveal a modular basis for distinct biochemical activities of viral RNA-dependent RNA polymerases.The Journal of biological chemistry · 2020Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The ability of an RNA virus to exist as a population of genetically distinct variants permits the virus to overcome events during infections that would otherwise limit virus multiplication or drive the population to extinction. Viral genetic diversity is created by the ribonucleotide misincorporation frequency of the viral RNA-dependent RNA polymerase (RdRp). We have identified a poliovirus (PV) RdRp derivative (H273R) possessing a mutator phenotype. GMP misincorporation efficiency for H273R RdRp in vitro was increased by 2-3-fold that manifested in a 2-3-fold increase in the diversity of the H273R PV population in cells. Circular sequencing analysis indicated that some mutations were RdRp-independent. Consistent with the population genetics theory, H273R PV was driven to extinction more easily than WT in cell culture. Furthermore, we observed a substantial reduction in H273R PV virulence, measured as the ability to cause paralysis in the cPVR mouse model. Reduced virulence correlated with the inability of H273R PV to sustain replication in tissues/organs in which WT persists. Despite the attenuated phenotype, H273R PV was capable of replicating in mice to levels sufficient to induce a protective immune response, even when the infecting dose used was insufficient to elicit any visual signs of infection. We conclude that optimal RdRp fidelity is a virulence determinant that can be targeted for viral attenuation or antiviral therapies, and we suggest that the RdRp may not be the only source of mutations in a RNA virus genome.
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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.