FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / PLoS One / Characterization of Genetic Variability of Venezuelan Equine...
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.
Get Full Text
Publication Date: 2016-04-07 PubMed ID: 27054586PubMed Central: PMC4824352DOI: 10.1371/journal.pone.0152604Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • 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.

References

This article includes 28 references
  1. Weaver SC, Ferro C, Barrera R, Boshell J, Navarro JC. Venezuelan equine encephalitis.. Annu Rev Entomol 2004;49:141-74.
    pubmed: 14651460doi: 10.1146/annurev.ento.49.061802.123422google scholar: lookup
  2. Quiroz E, Aguilar PV, Cisneros J, Tesh RB, Weaver SC. Venezuelan equine encephalitis in Panama: fatal endemic disease and genetic diversity of etiologic viral strains.. PLoS Negl Trop Dis 2009 Jun 30;3(6):e472.
    doi: 10.1371/journal.pntd.0000472pmc: PMC2697379pubmed: 19564908google scholar: lookup
  3. Vilcarromero S, Aguilar PV, Halsey ES, Laguna-Torres VA, Razuri H, Perez J, Valderrama Y, Gotuzzo E, Suarez L, Cespedes M, Kochel TJ. Venezuelan equine encephalitis and 2 human deaths, Peru.. Emerg Infect Dis 2010 Mar;16(3):553-6.
    doi: 10.3201/eid1603.090970pmc: PMC3322018pubmed: 20202445google scholar: lookup
  4. Johnson KM, Shelokov A, Peralta PH, Dammin GJ, Young NA. Recovery of Venezuelan equine encephalomyelitis virus in Panama. A fatal case in man.. Am J Trop Med Hyg 1968 May;17(3):432-40.
    pubmed: 5690051doi: 10.4269/ajtmh.1968.17.432google scholar: lookup
  5. Ferro C, Olano VA, Ahumada M, Weaver S. [Mosquitos (Diptera: Culicidae) in the small village where a human case of Venezuelan equine encephalitis was recorded].. Biomedica 2008 Jun;28(2):234-44.
    pubmed: 18719725
  6. Aguilar PV, Greene IP, Coffey LL, Medina G, Moncayo AC, Anishchenko M, Ludwig GV, Turell MJ, O'Guinn ML, Lee J, Tesh RB, Watts DM, Russell KL, Hice C, Yanoviak S, Morrison AC, Klein TA, Dohm DJ, Guzman H, Travassos da Rosa AP, Guevara C, Kochel T, Olson J, Cabezas C, Weaver SC. Endemic Venezuelan equine encephalitis in northern Peru.. Emerg Infect Dis 2004 May;10(5):880-8.
    doi: 10.3201/eid1005.030634pmc: PMC3323213pubmed: 15200823google scholar: lookup
  7. Forshey BM, Guevara C, Laguna-Torres VA, Cespedes M, Vargas J, Gianella A, Vallejo E, Madrid C, Aguayo N, Gotuzzo E, Suarez V, Morales AM, Beingolea L, Reyes N, Perez J, Negrete M, Rocha C, Morrison AC, Russell KL, Blair PJ, Olson JG, Kochel TJ. Arboviral etiologies of acute febrile illnesses in Western South America, 2000-2007.. PLoS Negl Trop Dis 2010 Aug 10;4(8):e787.
    doi: 10.1371/journal.pntd.0000787pmc: PMC2919378pubmed: 20706628google scholar: lookup
  8. Vilcarromero S, Laguna-Torres VA, Fernández C, Gotuzzo E, Suárez L, Céspedes M, Aguilar PV, Kochel TJ. Venezuelan equine encephalitis and upper gastrointestinal bleeding in child.. Emerg Infect Dis 2009 Feb;15(2):323-5.
    doi: 10.3201/eid1502.081018pmc: PMC2657634pubmed: 19193285google scholar: lookup
  9. Watts DM, Lavera V, Callahan J, Rossi C, Oberste MS, Roehrig JT, Cropp CB, Karabatsos N, Smith JF, Gubler DJ, Wooster MT, Nelson WM, Hayes CG. Venezuelan equine encephalitis and Oropouche virus infections among Peruvian army troops in the Amazon region of Peru.. Am J Trop Med Hyg 1997 Jun;56(6):661-7.
    pubmed: 9230800doi: 10.4269/ajtmh.1997.56.661google scholar: lookup
  10. Watts DM, Callahan J, Rossi C, Oberste MS, Roehrig JT, Wooster MT, Smith JF, Cropp CB, Gentrau EM, Karabatsos N, Gübler D, Hayes CG. Venezuelan equine encephalitis febrile cases among humans in the Peruvian Amazon River region.. Am J Trop Med Hyg 1998 Jan;58(1):35-40.
    pubmed: 9452289doi: 10.4269/ajtmh.1998.58.35google scholar: lookup
  11. Anishchenko M, Bowen RA, Paessler S, Austgen L, Greene IP, Weaver SC. Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation.. Proc Natl Acad Sci U S A 2006 Mar 28;103(13):4994-9.
    doi: 10.1073/pnas.0509961103pmc: PMC1458783pubmed: 16549790google scholar: lookup
  12. Brault AC, Powers AM, Holmes EC, Woelk CH, Weaver SC. Positively charged amino acid substitutions in the e2 envelope glycoprotein are associated with the emergence of venezuelan equine encephalitis virus.. J Virol 2002 Feb;76(4):1718-30.
    doi: 10.1128/JVI.76.4.1718-1730.2002pmc: PMC135911pubmed: 11799167google scholar: lookup
  13. Gardner S, Slezak T. Scalable SNP Analyses of 100+ Bacterial or Viral Genomes. J Forensic Res 2010;1:107.
    doi: 10.4172/2157-7145.1000107google scholar: lookup
  14. Gardner SN, Hall BG. When whole-genome alignments just won't work: kSNP v2 software for alignment-free SNP discovery and phylogenetics of hundreds of microbial genomes.. PLoS One 2013;8(12):e81760.
    doi: 10.1371/journal.pone.0081760pmc: PMC3857212pubmed: 24349125google scholar: lookup
  15. Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput.. Nucleic Acids Res 2004;32(5):1792-7.
    pmc: PMC390337pubmed: 15034147doi: 10.1093/nar/gkh340google scholar: lookup
  16. Price MN. Fast Tree-Comparison Tools Berkeley, CA. Available: http://meta.microbesonline.org/fasttree/treecmp.html.
  17. Huson DH, Scornavacca C. Dendroscope 3: an interactive tool for rooted phylogenetic trees and networks.. Syst Biol 2012 Dec 1;61(6):1061-7.
    doi: 10.1093/sysbio/sys062pubmed: 22780991google scholar: lookup
  18. Venkatachalam B, Apple J, St John K, Gusfield D. Untangling tanglegrams: comparing trees by their drawings.. IEEE/ACM Trans Comput Biol Bioinform 2010 Oct-Dec;7(4):588-97.
    doi: 10.1109/TCBB.2010.57pubmed: 20530818google scholar: lookup
  19. Gardner SN, Thissen JB, McLoughlin KS, Slezak T, Jaing CJ. Optimizing SNP microarray probe design for high accuracy microbial genotyping.. J Microbiol Methods 2013 Sep;94(3):303-10.
    doi: 10.1016/j.mimet.2013.07.006pubmed: 23871857google scholar: lookup
  20. Jaing C, Gardner S, McLoughlin K, Mulakken N, Alegria-Hartman M, Banda P, Williams P, Gu P, Wagner M, Manohar C, Slezak T. A functional gene array for detection of bacterial virulence elements.. PLoS One 2008 May 14;3(5):e2163.
    doi: 10.1371/journal.pone.0002163pmc: PMC2367441pubmed: 18478124google scholar: lookup
  21. Berge TO, Banks IS, Tigertt WD. Attenuation of Venezuelan equine encephalomyelitis virus by in vitro cultivation in guinea pig heart cells. Am J Hyg 1961;73:209–18.
  22. Team RC. R: A language and environment for statistical computing. 2014.
  23. Therneau T, Atkinson B, Ripley B, Oksanen J, De'ath G. mvpart: Multivariate partitioning. 2013.
  24. Venables W, Ripley B. Modern Applied Statistics with S. 4 ed. New York: Springer; 2002.
  25. Kolaczkowski B, Thornton JW. Performance of maximum parsimony and likelihood phylogenetics when evolution is heterogeneous.. Nature 2004 Oct 21;431(7011):980-4.
    pubmed: 15496922doi: 10.1038/nature02917google scholar: lookup
  26. Weaver SC, Barrett AD. Transmission cycles, host range, evolution and emergence of arboviral disease.. Nat Rev Microbiol 2004 Oct;2(10):789-801.
    doi: 10.1038/nrmicro1006pmc: PMC7097645pubmed: 15378043google scholar: lookup
  27. Weaver SC, Pfeffer M, Marriott K, Kang W, Kinney RM. Genetic evidence for the origins of Venezuelan equine encephalitis virus subtype IAB outbreaks.. Am J Trop Med Hyg 1999 Mar;60(3):441-8.
    pubmed: 10466974doi: 10.4269/ajtmh.1999.60.441google scholar: lookup
  28. Wolfe DN, Heppner DG, Gardner SN, Jaing C, Dupuy LC, Schmaljohn CS, Carlton K. Current strategic thinking for the development of a trivalent alphavirus vaccine for human use.. Am J Trop Med Hyg 2014 Sep;91(3):442-50.
    doi: 10.4269/ajtmh.14-0055pmc: PMC4155543pubmed: 24842880google scholar: lookup

Citations

This article has been cited 3 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
Subscribe to our newsletter
Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.