Evidence map›Paper›PMID 26114757›Full record

ArticlePLoS pathogens2015

Sequence-Specific Fidelity Alterations Associated with West Nile Virus Attenuation in Mosquitoes.

Greta A Van Slyke, Jamie J Arnold, Alex J Lugo, Sara B Griesemer, Ibrahim M Moustafa, Laura D Kramer, Craig E Cameron, Alexander T Ciota

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 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
10.3field-weighted citation impact, top 2% 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

55 citing papers in PubMed, 65 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. West Nile virus unmasked: from gene variability to future challenges.Frontiers in cellular and infection microbiology · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. The substitution spectra of coronavirus genomes.Briefings in bioinformatics · 2022
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

8 authors at 4 institutions in 1 country.

Greta A Van SlykeThe Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York, United States of America.
Jamie J ArnoldDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Alex J LugoDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Sara B GriesemerThe Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York, United States of America.
Ibrahim M MoustafaDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Laura D KramerThe Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York, United States of America; Department of Biomedical Sciences, State University of New York at Albany School of Public Health, Albany, New York, United States of America.
Craig E CameronDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Alexander T CiotaThe Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York, United States of America; Department of Biomedical Sciences, State University of New York at Albany School of Public Health, Albany, New York, United States of America.
Pennsylvania State University · USNew York State Department of Health · USUniversity at Albany, State University of New York · USWadsworth Center · US

Funding

Genetic determinants of adaptation of two flavivirusesR01AI077669 · NIAID · WADSWORTH CENTER · PI KRAMER, LAURA D · 2009 to 2013
$1.8M
NIAID NIH HHS R01 AI077669NIAID NIH HHS R01-AI-077669
6 · The paper itself

Abstract

High rates of error-prone replication result in the rapid accumulation of genetic diversity of RNA viruses. Recent studies suggest that mutation rates are selected for optimal viral fitness and that modest variations in replicase fidelity may be associated with viral attenuation. Arthropod-borne viruses (arboviruses) are unique in their requirement for host cycling and may necessitate substantial genetic and phenotypic plasticity. In order to more thoroughly investigate the correlates, mechanisms and consequences of arbovirus fidelity, we selected fidelity variants of West Nile virus (WNV; Flaviviridae, Flavivirus) utilizing selection in the presence of a mutagen. We identified two mutations in the WNV RNA-dependent RNA polymerase associated with increased fidelity, V793I and G806R, and a single mutation in the WNV methyltransferase, T248I, associated with decreased fidelity. Both deep-sequencing and in vitro biochemical assays confirmed strain-specific differences in both fidelity and mutational bias. WNV fidelity variants demonstrated host-specific alterations to replicative fitness in vitro, with modest attenuation in mosquito but not vertebrate cell culture. Experimental infections of colonized and field populations of Cx. quinquefaciatus demonstrated that WNV fidelity alterations are associated with a significantly impaired capacity to establish viable infections in mosquitoes. Taken together, these studies (i) demonstrate the importance of allosteric interactions in regulating mutation rates, (ii) establish that mutational spectra can be both sequence and strain-dependent, and (iii) display the profound phenotypic consequences associated with altered replication complex function of flaviviruses.

Indexed as

AnimalsBase SequenceCulicidaeGenetic VariationHost-Pathogen InteractionsMutationRNA-Dependent RNA PolymeraseVirus ReplicationWest Nile virusRNA-Dependent RNA Polymerase

Identifiers

PMID26114757
PMCPMC4482725
OpenAlexW763093762

What OpenQuestion holds

Textmetadata
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.