ArticleeLife2014
RNA virus attenuation by codon pair deoptimisation is an artefact of increases in CpG/UpA dinucleotide frequencies.
Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.
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
121 citing papers in PubMed, 1 synthesis or guideline pooled it, 176 citations in OpenAlex.
- Pooled it
- Transgene sequence codon optimization and composition determines replication competence of self-amplifying RNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- The genomic sequence of packaged viral ribonucleic acid predicts mucosal HIV-1 transmission fitness.iScience · 2026Article
- Increased or decreased numbers of CpG dinucleotide motifs in the genome of influenza A virus do not affectJournal of virology · 2026Article
- Multilayered nucleotide organization reveals purifying selection and host-driven adaptation in CPV and FPV.BMC veterinary research · 2026Article
- Single-cell transcriptomic profiling of bronchial lymph nodes reveals mechanisms of PRRSV escape from host adaptive immunity.Frontiers in immunology · 2026Article
- Effects of Korean red ginseng on the HIV-1Journal of ginseng research · 2026Article
- Differences in codon usage between host-species-specific rabies virus clades are driven by non-GC3 nucleotide composition.Virus evolution · 2026Article
- Review
- Mapping evolutionary paradigm of Oropouche virus driven by dinucleotide bias and context-dependent codon bias.Virulence · 2025Article
- Mapping evolutionary paradigm of bovine viral diarrhea virusVirulence · 2025Article
- Exploring CRISPR/Cas9-Mediated Gene Editing Advances in Conventional and Non-conventional Yeast Species.Applied biochemistry and biotechnology · 2025Review
- Understanding off-target growth defects introduced to influenza A virus by synonymous recoding.RNA (New York, N.Y.) · 2025Article
- West Nile virus vaccine candidates attenuated by dinucleotide enrichment are immunogenic and protective against lethal infection.PLoS pathogens · 2025Article
- Codon Usage Bias in Human RNA Viruses and Its Impact on Viral Translation, Fitness, and Evolution.Viruses · 2025Review
- Design and nonviral delivery of live attenuated vaccine to prevent chronic hepatitis C virus-like infection.Nature communications · 2025Article
- The mutational landscape of SARS-CoV-2 provides new insight into viral evolution and fitness.Nature communications · 2025Article
- Decoding codon usage in human papillomavirus type 59.Virus genes · 2025Article
- Adapted hepatitis C virus clone infects innate immunity-deficient mouse hepatocytes with minimal human HCV entry factors.JHEP reports : innovation in hepatology · 2025Article
- Article
61 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
5 authors at 3 institutions in 1 country.
Funding
Abstract
Mutating RNA virus genomes to alter codon pair (CP) frequencies and reduce translation efficiency has been advocated as a method to generate safe, attenuated virus vaccines. However, selection for disfavoured CPs leads to unintended increases in CpG and UpA dinucleotide frequencies that also attenuate replication. We designed and phenotypically characterised mutants of the picornavirus, echovirus 7, in which these parameters were independently varied to determine which most influenced virus replication. CpG and UpA dinucleotide frequencies primarily influenced virus replication ability while no fitness differences were observed between mutants with different CP usage where dinucleotide frequencies were kept constant. Contrastingly, translation efficiency was unaffected by either CP usage or dinucleotide frequencies. This mechanistic insight is critical for future rational design of live virus vaccines and their safety evaluation; attenuation is mediated through enhanced innate immune responses to viruses with elevated CpG/UpA dinucleotide frequencies rather the viruses themselves being intrinsically defective.
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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.