Evidence map›Paper›PMID 26325059›Full record

ArticlePLoS neglected tropical diseases2015

Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission.

Shuzhen Sim, Pauline P K Aw, Andreas Wilm, Garrett Teoh, Kien Duong Thi Hue, Nguyet Minh Nguyen, Niranjan Nagarajan, Cameron P Simmons, Martin L Hibberd

Abstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing 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

55 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. West Nile virus unmasked: from gene variability to future challenges.Frontiers in cellular and infection microbiology · 2025
    Review
  7. Article
  8. Article
  9. Envelope domain III EJournal of virology · 2024
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Intrinsic factors driving mosquito vector competence and viral evolution: a review.Frontiers in cellular and infection microbiology · 2023
    Review
  15. Article
  16. Intra-Host Diversity of Dengue Virus in Mosquito Vectors.Frontiers in cellular and infection microbiology · 2022
    Review
  17. Article
  18. UsingJournal of virology · 2021
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Shuzhen SimInfectious Diseases, Genome Institute of Singapore, Singapore, Singapore.
Pauline P K AwInfectious Diseases, Genome Institute of Singapore, Singapore, Singapore.
Andreas WilmInfectious Diseases, Genome Institute of Singapore, Singapore, Singapore.
Garrett TeohInfectious Diseases, Genome Institute of Singapore, Singapore, Singapore.
Kien Duong Thi HueOxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Nguyet Minh NguyenOxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Niranjan NagarajanInfectious Diseases, Genome Institute of Singapore, Singapore, Singapore.
Cameron P SimmonsOxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; Department of Microbiology and Immunology, University of Melbourne, Carlton, Victoria, Australia.
Martin L HibberdInfectious Diseases, Genome Institute of Singapore, Singapore, Singapore.

Funding

Wellcome Trust 084368/Z/07/ZWellcome Trust 089276
6 · The paper itself

Abstract

Dengue virus (DENV) infection of an individual human or mosquito host produces a dynamic population of closely-related sequences. This intra-host genetic diversity is thought to offer an advantage for arboviruses to adapt as they cycle between two very different host species, but it remains poorly characterized. To track changes in viral intra-host genetic diversity during horizontal transmission, we infected Aedes aegypti mosquitoes by allowing them to feed on DENV2-infected patients. We then performed whole-genome deep-sequencing of human- and matched mosquito-derived DENV samples on the Illumina platform and used a sensitive variant-caller to detect single nucleotide variants (SNVs) within each sample. >90% of SNVs were lost upon transition from human to mosquito, as well as from mosquito abdomen to salivary glands. Levels of viral diversity were maintained, however, by the regeneration of new SNVs at each stage of transmission. We further show that SNVs maintained across transmission stages were transmitted as a unit of two at maximum, suggesting the presence of numerous variant genomes carrying only one or two SNVs each. We also present evidence for differences in selection pressures between human and mosquito hosts, particularly on the structural and NS1 genes. This analysis provides insights into how population drops during transmission shape RNA virus genetic diversity, has direct implications for virus evolution, and illustrates the value of high-coverage, whole-genome next-generation sequencing for understanding viral intra-host genetic diversity.

Indexed as

Genetic VariationAdultAedesAnimalsDengueDengue VirusFemaleGastrointestinal TractHigh-Throughput Nucleotide SequencingHumansMalePolymorphism, Single NucleotideRNA, ViralSalivary GlandsSelection, GeneticViral Nonstructural ProteinsNS1 protein, Dengue virus type 2RNA, ViralViral Nonstructural Proteins

Identifiers

PMID26325059
PMCPMC4556672

What OpenQuestion holds

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LicenceCC BY
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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.