ArticleNucleic acids research2014
The influence of CpG and UpA dinucleotide frequencies on RNA virus replication and characterization of the innate cellular pathways underlying virus attenuation and enhanced replication.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 1 of them a synthesis that pooled it.
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Who cites it
126 citing papers in PubMed, 1 synthesis or guideline pooled it, 193 citations in OpenAlex.
- Synonymous but Not Silent: The Codon Usage Code for Gene Expression and Protein Folding.Annual review of biochemistry · 2021Pooled 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
- Divergent host adaptation in Marburg virus: a hypothesis-generating framework for prioritizing non-traditional reservoirs.BMC genomics · 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
- Effects of Korean red ginseng on the HIV-1Journal of ginseng research · 2026Article
- Single-cell transcriptomic profiling of bronchial lymph nodes reveals mechanisms of PRRSV escape from host adaptive immunity.Frontiers in immunology · 2026Article
- Predicting host tropism in influenza a viruses: insights from multi-segment nucleotide signatures.Journal of translational medicine · 2025Article
- RNA editing signatures and codon adaptation reveal potential translational compatibility between Hendra virus and its natural host Pteropus Alecto.Archives of microbiology · 2025Article
- Mapping evolutionary paradigm of bovine viral diarrhea virusVirulence · 2025Article
- Effect of increased CpG and UpA dinucleotides in the West Nile virus genome on virus transmission byJournal of virology · 2025Article
- Understanding off-target growth defects introduced to influenza A virus by synonymous recoding.RNA (New York, N.Y.) · 2025Article
- Mammalian antiviral proteins ZAP and KHNYN can independently restrict CpG-enriched avian viruses.PLoS biology · 2025Article
- West Nile virus vaccine candidates attenuated by dinucleotide enrichment are immunogenic and protective against lethal infection.PLoS pathogens · 2025Article
- Mammalian ZAP and KHNYN can independently restrict CpG-enriched avian viruses.bioRxiv : the preprint server for biology · 2025Article
- Measuring the selective packaging of RNA molecules by viral coat proteins in cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Deciphering the Code of Viral-Host Adaptation Through Maximum-Entropy Nucleotide Bias Models.Molecular biology and evolution · 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
66 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
4 authors at 3 institutions in 1 country.
Funding
Abstract
Most RNA viruses infecting mammals and other vertebrates show profound suppression of CpG and UpA dinucleotide frequencies. To investigate this functionally, mutants of the picornavirus, echovirus 7 (E7), were constructed with altered CpG and UpA compositions in two 1.1-1.3 Kbase regions. Those with increased frequencies of CpG and UpA showed impaired replication kinetics and higher RNA/infectivity ratios compared with wild-type virus. Remarkably, mutants with CpGs and UpAs removed showed enhanced replication, larger plaques and rapidly outcompeted wild-type virus on co-infections. Luciferase-expressing E7 sub-genomic replicons with CpGs and UpAs removed from the reporter gene showed 100-fold greater luminescence. E7 and mutants were equivalently sensitive to exogenously added interferon-β, showed no evidence for differential recognition by ADAR1 or pattern recognition receptors RIG-I, MDA5 or PKR. However, kinase inhibitors roscovitine and C16 partially or entirely reversed the attenuated phenotype of high CpG and UpA mutants, potentially through inhibition of currently uncharacterized pattern recognition receptors that respond to RNA composition. Generating viruses with enhanced replication kinetics has applications in vaccine production and reporter gene construction. More fundamentally, the findings introduce a new evolutionary paradigm where dinucleotide composition of viral genomes is subjected to selection pressures independently of coding capacity and profoundly influences host-pathogen interactions.
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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.