Evidence map›Paper›PMID 25157129›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Attenuation of human respiratory syncytial virus by genome-scale codon-pair deoptimization.

Cyril Le Nouën, Linda G Brock, Cindy Luongo, Thomas McCarty, Lijuan Yang, Masfique Mehedi, Eckard Wimmer, Steffen Mueller, Peter L Collins, Ursula J Buchholz and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 125 citations in OpenAlex.

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  12. Human parainfluenza virus 3 vaccine candidates attenuated by codon-pair deoptimization are immunogenic and protective in hamsters.Proceedings of the National Academy of Sciences of the United States of America · 2024
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25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Cyril Le NouënRNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and lenouenc@niaid.nih.gov Eckard.Wimmer@stonybrook.edu.
Linda G BrockRNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
Cindy LuongoRNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
Thomas McCartyRNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
Lijuan YangRNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
Masfique MehediRNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
Eckard WimmerDepartment of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794 lenouenc@niaid.nih.gov Eckard.Wimmer@stonybrook.edu.
Steffen MuellerDepartment of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794.
Peter L CollinsRNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
Ursula J BuchholzRNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
Joshua M DiNapoliRNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
National Institutes of Health · USNational Institute of Allergy and Infectious Diseases · USStony Brook University · US

Funding

Laboratory Studies of Human Respiratory Syncytial Virus and Other PneumovirusesZIAAI000372 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BUCHHOLZ, URSULA · 2009 to 2025
$21.8M
Intramural NIH HHSNIAID NIH HHS R01 AI07521901
6 · The paper itself

Abstract

Human respiratory syncytial virus (RSV) is the most important viral agent of serious pediatric respiratory-tract disease worldwide. A vaccine or generally effective antiviral drug is not yet available. We designed new live attenuated RSV vaccine candidates by codon-pair deoptimization (CPD). Specifically, viral ORFs were recoded by rearranging existing synonymous codons to increase the content of underrepresented codon pairs. Amino acid coding was completely unchanged. Four CPD RSV genomes were designed in which the indicated ORFs were recoded: Min A (NS1, NS2, N, P, M, and SH), Min B (G and F), Min L (L), and Min FLC (all ORFs except M2-1 and M2-2). Surprisingly, the recombinant CPD viruses were temperature-sensitive for replication in vitro (level of sensitivity: Min FLC > Min L > Min B > Min A). All of the CPD mutants grew less efficiently in vitro than recombinant wild-type (WT) RSV, even at the typically permissive temperature of 32 °C (growth efficiency: WT > Min L > Min A > Min FLC > Min B). CPD of the ORFs for the G and F surface glycoproteins provided the greatest restrictive effect. The CPD viruses exhibited a range of restriction in mice and African green monkeys comparable with that of two attenuated RSV strains presently in clinical trials. This study provided a new type of attenuated RSV and showed that CPD can rapidly generate vaccine candidates against nonsegmented negative-strand RNA viruses, a large and expanding group that includes numerous pathogens of humans and animals.

Indexed as

AnimalsCells, CulturedChlorocebus aethiopsCodonGenome, ViralHumansMice, Inbred BALB CMolecular Sequence DataNasopharynxRecombination, GeneticRespiratory Syncytial Virus, HumanRNA, ViralTemperatureVero CellsViral ProteinsVirus ReplicationCodonRNA, ViralViral Proteinslive attenuated vaccinenegative strand RNA viruspneumovirus

Identifiers

PMID25157129
PMCPMC4246931
OpenAlexW4230166999

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.