ArticlePLoS pathogens2023
CpG dinucleotide enrichment in the influenza A virus genome as a live attenuated vaccine development strategy.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
- Balancing Genome Plasticity and Evolutionary Constraint During the Long-Term Evolution of Feline Coronaviruses.Viruses · 2026Article
- Increased or decreased numbers of CpG dinucleotide motifs in the genome of influenza A virus do not affectJournal of virology · 2026Article
- Synthetic Biology Strategies for the Development of Live Attenuated Influenza Viruses: Recent Advances and Applications.Viruses · 2026Review
- SPRY domains encode ubiquitin ligase specificity for ZAP and RIG-I.PLoS pathogens · 2026Article
- Genome-Wide Codon Reprogramming Enables a Multifactorially Attenuated Influenza Vaccine with Broad Cross-Protection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Broad beta-CoV immunity and transmission blockade by a single-dose live-attenuated vaccine with atypical codon usage.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Differences in codon usage between host-species-specific rabies virus clades are driven by non-GC3 nucleotide composition.Virus evolution · 2026Article
- Mapping evolutionary paradigm of bovine viral diarrhea virusVirulence · 2025Article
- ARCADE: Controllable Codon Design from Foundation Models via Activation Engineering.bioRxiv : the preprint server for biology · 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
- West Nile virus vaccine candidates attenuated by dinucleotide enrichment are immunogenic and protective against lethal infection.PLoS pathogens · 2025Article
- Mammalian antiviral proteins ZAP and KHNYN can independently restrict CpG-enriched avian viruses.PLoS biology · 2025Article
- Mammalian ZAP and KHNYN can independently restrict CpG-enriched avian viruses.bioRxiv : the preprint server for biology · 2025Article
- HIV-2 evades restriction by ZAP through adaptations in the U3 LTR region despite increased CpG levels.Nucleic acids research · 2025Article
- Codon-deoptimized single-round infectious virus for therapeutic and vaccine applications.Scientific reports · 2025Article
- Decoding codon usage in human papillomavirus type 59.Virus genes · 2025Article
- Article
- Selection on synonymous sites: the unwanted transcript hypothesis.Nature reviews. Genetics · 2024Review
- Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Synonymous recoding of RNA virus genomes is a promising approach for generating attenuated viruses to use as vaccines. Problematically, recoding typically hinders virus growth, but this may be rectified using CpG dinucleotide enrichment. CpGs are recognised by cellular zinc-finger antiviral protein (ZAP), and so in principle, removing ZAP sensing from a virus propagation system will reverse attenuation of a CpG-enriched virus, enabling high titre yield of a vaccine virus. We tested this using a vaccine strain of influenza A virus (IAV) engineered for increased CpG content in genome segment 1. Virus attenuation was mediated by the short isoform of ZAP, correlated with the number of CpGs added, and was enacted via turnover of viral transcripts. The CpG-enriched virus was strongly attenuated in mice, yet conveyed protection from a potentially lethal challenge dose of wildtype virus. Importantly for vaccine development, CpG-enriched viruses were genetically stable during serial passage. Unexpectedly, in both MDCK cells and embryonated hens' eggs that are used to propagate live attenuated influenza vaccines, the ZAP-sensitive virus was fully replication competent. Thus, ZAP-sensitive CpG enriched viruses that are defective in human systems can yield high titre in vaccine propagation systems, providing a realistic, economically viable platform to augment existing live attenuated vaccines.
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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.