Evidence map›Paper›PMID 30192757›Full record

ArticlePloS one2018

Extensive recoding of dengue virus type 2 specifically reduces replication in primate cells without gain-of-function in Aedes aegypti mosquitoes.

Charles B Stauft, Sam H Shen, Yutong Song, Oleksandr Gorbatsevych, Emmanuel Asare, Bruce Futcher, Steffen Mueller, Anne Payne, Matthew Brecher, Laura Kramer and 1 more

Abstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

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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.

Charles B StauftStony Brook University, Department of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, New York, United States of America.
Sam H ShenStony Brook University, Department of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, New York, United States of America.
Yutong SongStony Brook University, Department of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, New York, United States of America.
Oleksandr GorbatsevychStony Brook University, Department of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, New York, United States of America.ORCID 0000-0002-2159-1490
Emmanuel AsareStony Brook University, Department of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, New York, United States of America.
Bruce FutcherStony Brook University, Department of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, New York, United States of America.
Steffen MuellerStony Brook University, Department of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, New York, United States of America.
Anne PayneWadsworth Center, New York State Department of Health, Slingerlands, New York, United States of America.
Matthew BrecherWadsworth Center, New York State Department of Health, Slingerlands, New York, United States of America.ORCID 0000-0003-1151-2290
Laura KramerWadsworth Center, New York State Department of Health, Slingerlands, New York, United States of America.
Eckard WimmerStony Brook University, Department of Molecular Genetics and Microbiology, Stony Brook University School of Medicine, Stony Brook, New York, United States of America.

Funding

Tailoring virulence of dengue virus in mammals and mosquitoesR01AI110792 · NIAID · STATE UNIVERSITY NEW YORK STONY BROOK · PI WIMMER, ECKARD · 2015 to 2018
$2.2M
Encoding biases and their effects on translation, quality control and gene expressionR01GM119175 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI FUTCHER, BRUCE BRUCE · 2016 to 2019
$1.2M
Chikungunya vaccine candidate developed by codon pair de-optimizationR21AI126048 · NIAID · STATE UNIVERSITY NEW YORK STONY BROOK · PI SONG, YUTONG · 2016 to 2017
$436k
NIAID NIH HHS R01 AI110792NIAID NIH HHS R21 AI126048NIGMS NIH HHS R01 GM119175
6 · The paper itself

Abstract

Dengue virus (DENV), an arthropod-borne ("arbovirus") virus, causes a range of human maladies ranging from self-limiting dengue fever to the life-threatening dengue shock syndrome and proliferates well in two different taxa of the Animal Kingdom, mosquitoes and primates. Mosquitoes and primates show taxonomic group-specific intolerance to certain codon pairs when expressing their genes by translation. This is called "codon pair bias". By necessity, dengue viruses evolved to delicately balance this fundamental difference in their open reading frames (ORFs). We have undone the evolutionarily conserved genomic balance in the DENV2 ORF sequence and specifically shifted the encoding preference away from primates. However, this recoding of DENV2 raised concerns of 'gain-of-function,' namely whether recoding could inadvertently increase fitness for replication in the arthropod vector. Using mosquito cell lines and two strains of Aedes aegypti we did not observe any increase in fitness in DENV2 variants codon pair deoptimized for humans. This ability to disrupt and control DENV2's host preference has great promise towards developing the next generation of synthetic vaccines not only for DENV but for other emerging arboviral pathogens such as chikungunya virus and Zika virus.

Indexed as

Genome, ViralAedesAnimalsCell LineChlorocebus aethiopsDengue VirusVero CellsVirus Replication

Identifiers

PMID30192757
PMCPMC6128446

What OpenQuestion holds

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LicenceCC BY
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.