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PloS one2016; 11(4); e0152604; doi: 10.1371/journal.pone.0152604

Characterization of Genetic Variability of Venezuelan Equine Encephalitis Viruses.

Abstract: Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne alphavirus that has caused large outbreaks of severe illness in both horses and humans. New approaches are needed to rapidly infer the origin of a newly discovered VEEV strain, estimate its equine amplification and resultant epidemic potential, and predict human virulence phenotype. We performed whole genome single nucleotide polymorphism (SNP) analysis of all available VEE antigenic complex genomes, verified that a SNP-based phylogeny accurately captured the features of a phylogenetic tree based on multiple sequence alignment, and developed a high resolution genome-wide SNP microarray. We used the microarray to analyze a broad panel of VEEV isolates, found excellent concordance between array- and sequence-based SNP calls, genotyped unsequenced isolates, and placed them on a phylogeny with sequenced genomes. The microarray successfully genotyped VEEV directly from tissue samples of an infected mouse, bypassing the need for viral isolation, culture and genomic sequencing. Finally, we identified genomic variants associated with serotypes and host species, revealing a complex relationship between genotype and phenotype.
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Publication Date: 2016-04-07 PubMed ID: 27054586PubMed Central: PMC4824352DOI: 10.1371/journal.pone.0152604Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research study focuses on the Venezuelan equine encephalitis virus (VEEV), a mosquito-borne virus affecting both humans and horses. The scientists developed a method to quickly determine the origin and potential epidemic ability of newly discovered VEEV strains by studying single nucleotide polymorphisms (SNPs) in the virus genome.

Research Methods

  • The global genetic variation of Venezuelan equine encephalitis viruses (VEEV) was analyzed through whole genome single nucleotide polymorphism (SNP) study moderated across every accessible VEEV antigenic complex genome.
  • The research team then verified whether a SNP-based phylogeny accurately portrayed the characteristics of a phylogenetic tree derived through multiple sequence alignment.
  • A comprehensive genome-wide SNP microarray was developed, which played a key role in facilitating further stages of the research study.

Analyzing VEEV isolates

  • The team employed the microarray to analyze a wide variety of VEEV isolates. They compared the SNP calls generated by the array and sequencing methods and found that they matched excellently.
  • The array was used to identify the genotypes of previously unsequenced isolates and their data was integrated on a phylogeny with sequenced genomes.
  • The microarray was even capable of directly genotyping VEEV from tissue samples of an infected mouse which eliminated the need for viral isolation, culture and genomic sequencing.

Identifying Genomic Variants

  • In the final stages of the research, the team identified specific genomic variations associated with serotypes and host species. Such analysis highlighted a complex relationship between the genotype of VEEV and the phenotype, or the observable characteristics in the host.
  • The discovery of these genetic variations can potentially predict the virulence phenotype in humans i.e., the severity of the disease caused by VEEV.

Significance of the Study

  • This research presents a system for quickly inferring the origin of a newly discovered VEEV strain, and its potential for causing an epidemic.
  • The SNP microarray developed can also be used in other future studies to identify and analyze genomic variants of VEEV.
  • Further understanding of the genomic variability of VEEV can have significant implications in vaccine development and outbreak control.

Cite This Article

APA
Gardner SN, McLoughlin K, Be NA, Allen J, Weaver SC, Forrester N, Guerbois M, Jaing C. (2016). Characterization of Genetic Variability of Venezuelan Equine Encephalitis Viruses. PLoS One, 11(4), e0152604. https://doi.org/10.1371/journal.pone.0152604

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 11
Issue: 4
Pages: e0152604
PII: e0152604

Researcher Affiliations

Gardner, Shea N
  • Computations, Lawrence Livermore National Laboratory, Livermore, California, United States of America.
McLoughlin, Kevin
  • Computations, Lawrence Livermore National Laboratory, Livermore, California, United States of America.
Be, Nicholas A
  • Physical and Life Sciences, Lawrence Livermore National Laboratory, Livermore, California, United States of America.
Allen, Jonathan
  • Computations, Lawrence Livermore National Laboratory, Livermore, California, United States of America.
Weaver, Scott C
  • Institute for Human Infections and Immunity and Departments of Microbiology & Immunology and Pathology, University of Texas, Medical Branch, Galveston, Texas, United States of America.
Forrester, Naomi
  • Institute for Human Infections and Immunity and Departments of Microbiology & Immunology and Pathology, University of Texas, Medical Branch, Galveston, Texas, United States of America.
Guerbois, Mathilde
  • Institute for Human Infections and Immunity and Departments of Microbiology & Immunology and Pathology, University of Texas, Medical Branch, Galveston, Texas, United States of America.
Jaing, Crystal
  • Physical and Life Sciences, Lawrence Livermore National Laboratory, Livermore, California, United States of America.

MeSH Terms

  • Animals
  • Cricetinae / virology
  • Culicidae / virology
  • Encephalitis Virus, Venezuelan Equine / genetics
  • Encephalitis Virus, Venezuelan Equine / isolation & purification
  • Encephalomyelitis, Venezuelan Equine / epidemiology
  • Genetic Variation
  • Genome, Viral
  • Genotype
  • Host-Pathogen Interactions / genetics
  • Mexico / epidemiology
  • Mice, Inbred Strains / virology
  • Oligonucleotide Array Sequence Analysis / methods
  • Phenotype
  • Phylogeny
  • Polymorphism, Single Nucleotide

Grant Funding

  • R24 AI120942 / NIAID NIH HHS

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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Citations

This article has been cited 5 times.
  1. Guzmán C, Calderón A, Oviedo T, Mattar S, Castañeda J, Rodriguez V, Moraes Figueiredo LT. Molecular and cellular evidence of natural Venezuelan equine encephalitis virus infection in frugivorous bats in Colombia. Vet World 2020 Mar;13(3):495-501.
    doi: 10.14202/vetworld.2020.495-501pubmed: 32367955google scholar: lookup
  2. Gim JA, Kwon Y, Lee HA, Lee KR, Kim S, Choi Y, Kim YK, Lee H. A Machine Learning-Based Identification of Genes Affecting the Pharmacokinetics of Tacrolimus Using the DMET(TM) Plus Platform. Int J Mol Sci 2020 Apr 4;21(7).
    doi: 10.3390/ijms21072517pubmed: 32260456google scholar: lookup
  3. Guzmán C, Calderón A, Martinez C, Oviedo M, Mattar S. Eco-epidemiology of the Venezuelan equine encephalitis virus in bats of Córdoba and Sucre, Colombia. Acta Trop 2019 Mar;191:178-184.
    doi: 10.1016/j.actatropica.2018.12.016pubmed: 30578748google scholar: lookup
  4. Hickson SE, Hyde JL. RNA structures within Venezuelan equine encephalitis virus E1 alter macrophage replication fitness and contribute to viral emergence. PLoS Pathog 2024 Sep;20(9):e1012179.
    doi: 10.1371/journal.ppat.1012179pubmed: 39331659google scholar: lookup
  5. Hickson SE, Hyde JL. RNA structures within Venezuelan equine encephalitis virus E1 alter macrophage replication fitness and contribute to viral emergence. bioRxiv 2024 Apr 9;.
    doi: 10.1101/2024.04.09.588743pubmed: 38645187google scholar: lookup
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