Evidence map›Paper›PMID 31611100›Full record

ArticleVaccine2019

Genotypic and phenotypic characterization of West Nile virus NS5 methyltransferase mutants.

Jaclyn A Kaiser, Huanle Luo, Steven G Widen, Thomas G Wood, Claire Y-H Huang, Tian Wang, Alan D T Barrett

Open access · greenAbstract read
In one paragraph

Article in Vaccine, 2019. 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
1.1field-weighted citation impact, top 20% 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

8 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Replication Kinetics of a Candidate Live-Attenuated Vaccine for Cache Valley Virus inVector borne and zoonotic diseases (Larchmont, N.Y.) · 2022
    Article
  5. Review
  6. Article
  7. Article
  8. Review
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

7 authors at 2 institutions in 1 country.

Jaclyn A KaiserDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, United States.
Huanle LuoDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, United States.
Steven G WidenMolecular Genomics Core Facility, University of Texas Medical Branch, Galveston, TX 77555, United States.
Thomas G WoodMolecular Genomics Core Facility, University of Texas Medical Branch, Galveston, TX 77555, United States.
Claire Y-H HuangDivision of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, United States.
Tian WangDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, United States; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, United States; Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, United States.
Alan D T BarrettDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, United States; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, United States; Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, United States. Electronic address: abarrett@utmb.edu.
The University of Texas Medical Branch at Galveston · USCenters for Disease Control and Prevention · US

Funding

EMERGING AND TROPICAL INFECTIOUS DISEASEST32AI007526 · NIAID · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI SOONG, LYNN · 1997 to 2025
$3.1M
Rational Development of Candidate Attenuated Flavivirus VaccinesR01AI099123 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI WANG, TIAN · 2013 to 2016
$1.8M
Intramural CDC HHS CC999999NIAID NIH HHS R01 AI099123NIAID NIH HHS T32 AI007526
6 · The paper itself

Abstract

Although West Nile virus (WNV) causes annual cases of neurological disease and deaths in humans, a vaccine has not been licensed for human use. Several WNV genes have been targeted for mutagenesis in attempts to generate live attenuated vaccine candidates, including the non-structural protein NS5. Specifically, mutation of WNV NS5-K61A or NS5-E218A in the catalytic tetrad of the methyltransferase decreases enzyme activity of the NS5 protein and correspondingly attenuates the virus in mice. In this report, NS5-K61A, NS5-E218A, and a double mutant encoding both mutations (NS5-K61A/E218A) were compared both in vitro and in vivo. Each single mutant was strongly attenuated in highly susceptible outbred mice, whereas the double mutant unexpectedly was not attenuated. Sequencing analysis demonstrated that the double mutant was capable of reversion at both residues NS5-61 and NS5-218, whereas the genotype of the single mutants did not show evidence of reversion. Overall, either NS5-K61A or NS5-E218A methyltransferase mutations could be potential mutations to include in a candidate live WNV vaccine; however, multiple mutations in the catalytic tetrad of the methyltransferase are not tolerated.

Indexed as

GenotypeMutationAnimalsCell LineCytokinesFemaleHumansMiceModels, MolecularProtein ConformationStructure-Activity RelationshipViral Nonstructural ProteinsWest Nile FeverWest Nile virusCytokinesNS5 protein, flavivirusViral Nonstructural ProteinsAttenuationFlavivirusMethyltransferaseNS5 proteinWest Nile virus

Identifiers

PMID31611100
PMCPMC6996054
OpenAlexW2980246318

What OpenQuestion holds

Textmetadata
LicenceTDM
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.