Analyze Diet
Veterinary sciences2022; 9(6); 258; doi: 10.3390/vetsci9060258

Phylogenetic and Mutation Analysis of the Venezuelan Equine Encephalitis Virus Sequence Isolated in Costa Rica from a Mare with Encephalitis.

Abstract: Venezuelan Equine Encephalitis virus (VEEV) is an arboviral pathogen in tropical America that causes lethal encephalitis in horses and humans. VEEV is classified into six subtypes (I to VI). Subtype I viruses are divided into epizootic (IAB and IC) and endemic strains (ID and IE) that can produce outbreaks or sporadic diseases, respectively. The objective of this study was to reconstruct the phylogeny and the molecular clock of sequences of VEEV subtype I complex and identify mutations within sequences belonging to epizootic or enzootic subtypes focusing on a sequence isolated from a mare in Costa Rica. Bayesian phylogeny of the VEEV subtype I complex tree with 110 VEEV complete genomes was analyzed. Evidence of positive selection was evaluated with Datamonkey server algorithms. The putative effects of mutations on the 3D protein structure in the Costa Rica sequence were evaluated. The phylogenetic analysis showed that Subtype IE-VEEV diverged earlier than other subtypes, Costa Rican VEEV-IE ancestors came from Nicaragua in 1963 and Guatemala in 1907. Among the observed non-synonymous mutations, only 17 amino acids changed lateral chain groups. Fourteen mutations located in the NSP3, E1, and E2 genes are unique in this sequence, highlighting the importance of E1-E2 genes in VEEV evolution.
Publication Date: 2022-05-28 PubMed ID: 35737310PubMed Central: PMC9229380DOI: 10.3390/vetsci9060258Google 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.
  • Journal Article

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.

The research attempts to understand the phylogeny and molecular clock of Venezuelan Equine Encephalitis Virus (VEEV) subtype I complex and identify mutations in specific sequences. Particular focus was given to a sequence isolated from a mare in Costa Rica. The findings show the evolution and divergence of the virus over time while identifying specific non-synonymous mutations in certain genes unique to this sequence.

Objective of the Study

  • The main aim of the study was to understand the evolution and mutation patterns of the Venezuelan Equine Encephalitis Virus (VEEV) subtype I complex. This involved analyzing the phylogeny and molecular clock of the virus.
  • A key focus of the research was an examination of a sequence of the virus that was isolated from a mare in Costa Rica. The researchers aimed to identify any mutations in this sequence.

Methods and Analysis

  • The researchers reconstructed the Bayesien phylogeny of the VEEV subtype I complex tree using 110 complete VEEV genomes.
  • Positive selection, which is a key process in evolution, was evaluated using Datamonkey server algorithms.
  • The putative effects of the identified mutations on the 3D protein structure within the Costa Rican sequence were also evaluated. This helped to understand how these mutations might impact the functionality of the virus.

Research Findings

  • The phylogenetic analysis revealed that the Subtype IE-VEEV diverged earlier than the other subtypes, with the Costa Rican VEEV-IE ancestors traced back to Nicaragua in 1963 and Guatemala in 1907.
  • The researchers found non-synonymous mutations (mutations that alter the amino acid sequence of a protein) with only 17 amino acids changing their lateral chain groups.
  • Out of these, 14 mutations were unique to the sequence isolated from the mare in Costa Rica. These mutations were located in the NSP3, E1 and E2 genes, underscoring the role these genes might play in VEEV evolution.

Implications of the Study

  • This kind of genetic and phylogenetic understanding can play a fundamental role in predicting the possible evolution and spread of the virus.
  • The identification of unique mutations in specific genes also provides potential targets for diagnostics, treatment, and vaccines for this pathogen.

Cite This Article

APA
León B, González G, Nicoli A, Rojas A, Pizio AD, Ramirez-Carvajal L, Jimenez C. (2022). Phylogenetic and Mutation Analysis of the Venezuelan Equine Encephalitis Virus Sequence Isolated in Costa Rica from a Mare with Encephalitis. Vet Sci, 9(6), 258. https://doi.org/10.3390/vetsci9060258

Publication

ISSN: 2306-7381
NlmUniqueID: 101680127
Country: Switzerland
Language: English
Volume: 9
Issue: 6
PII: 258

Researcher Affiliations

León, Bernal
  • LSE Laboratory, Veterinary Service National Laboratory, Animal Health National Service, Ministry of Agriculture and Cattle, Heredia 40104, Costa Rica.
  • Virology, Universidad Técnica Nacional (UTN), Atenas 20505, Costa Rica.
González, Gabriel
  • National Virus Reference Laboratory, College Dublin, D04 V1W8 Belfield, Ireland.
Nicoli, Alessandro
  • Leibniz Institute for Food Systems Biology at the Technical University of Munich, 85354 Freising, Germany.
Rojas, Alicia
  • Laboratory of Helminthology, Centro de Investigación en Enfermedades Tropicales, University of Costa Rica, San José 11501, Costa Rica.
Pizio, Antonella Di
  • Leibniz Institute for Food Systems Biology at the Technical University of Munich, 85354 Freising, Germany.
Ramirez-Carvajal, Lisbeth
  • Veterinary Medicine Infection and Immunity, Virology, University of Utrecht, 3584 CS Utrecht, The Netherlands.
Jimenez, Carlos
  • Laboratory of Virology, Tropical Diseases Research Program (PIET), School of Veterinary Medicine, Universidad Nacional, Heredia 40101, Costa Rica.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 49 references
  1. Martin DH, Eddy GA, Sudia WD, Reeves WC, Newhouse VF, Johnson KM. An epidemiologic study of Venezuelan equine encephalomyelitis in Costa Rica, 1970.. Am J Epidemiol 1972 Jun;95(6):565-78.
  2. Estrada-Franco JG, Navarro-Lopez R, Freier JE, Cordova D, Clements T, Moncayo A, Kang W, Gomez-Hernandez C, Rodriguez-Dominguez G, Ludwig GV, Weaver SC. Venezuelan equine encephalitis virus, southern Mexico.. Emerg Infect Dis 2004 Dec;10(12):2113-21.
    doi: 10.3201/eid1012.040393pmc: PMC3323369pubmed: 15663847google scholar: lookup
  3. Guzmán-Terán C, Calderón-Rangel A, Rodriguez-Morales A, Mattar S. Venezuelan equine encephalitis virus: the problem is not over for tropical America.. Ann Clin Microbiol Antimicrob 2020 May 19;19(1):19.
    doi: 10.1186/s12941-020-00360-4pmc: PMC7236962pubmed: 32429942google scholar: lookup
  4. Lord RD. [Venezuelan equine encephalitis. Its history and geographic distribution].. Bol Oficina Sanit Panam 1973 Dec;75(6):530-41.
    pubmed: 4273163
  5. Kubes V, Ríos FA. THE CAUSATIVE AGENT OF INFECTIOUS EQUINE ENCEPHALOMYELITIS IN VENEZUELA.. Science 1939 Jul 7;90(2323):20-1.
    doi: 10.1126/science.90.2323.20pubmed: 17818578google scholar: lookup
  6. Strauss JH, Strauss EG. The alphaviruses: gene expression, replication, and evolution.. Microbiol Rev 1994 Sep;58(3):491-562.
    doi: 10.1128/mr.58.3.491-562.1994pmc: PMC372977pubmed: 7968923google scholar: lookup
  7. Forrester NL, Wertheim JO, Dugan VG, Auguste AJ, Lin D, Adams AP, Chen R, Gorchakov R, Leal G, Estrada-Franco JG, Pandya J, Halpin RA, Hari K, Jain R, Stockwell TB, Das SR, Wentworth DE, Smith MD, Kosakovsky Pond SL, Weaver SC. Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas.. PLoS Negl Trop Dis 2017 Aug;11(8):e0005693.
  8. Powers AM, Oberste MS, Brault AC, Rico-Hesse R, Schmura SM, Smith JF, Kang W, Sweeney WP, Weaver SC. Repeated emergence of epidemic/epizootic Venezuelan equine encephalitis from a single genotype of enzootic subtype ID virus.. J Virol 1997 Sep;71(9):6697-705.
  9. Oberste MS, Schmura SM, Weaver SC, Smith JF. Geographic distribution of Venezuelan equine encephalitis virus subtype IE genotypes in Central America and Mexico.. Am J Trop Med Hyg 1999 Apr;60(4):630-4.
    doi: 10.4269/ajtmh.1999.60.630pubmed: 10348239google scholar: lookup
  10. Franck PT, Johnson KM. An outbreak of Venezuelan equine encephalomeylitis in Central America. Evidence for exogenous source of a virulent virus subtype.. Am J Epidemiol 1971 Nov;94(5):487-95.
  11. Aguilar PV, Estrada-Franco JG, Navarro-Lopez R, Ferro C, Haddow AD, Weaver SC. Endemic Venezuelan equine encephalitis in the Americas: hidden under the dengue umbrella.. Future Virol 2011;6(6):721-740.
    doi: 10.2217/fvl.11.50pmc: PMC3134406pubmed: 21765860google scholar: lookup
  12. Fuentes LG. [Serological study of group A Arbovirus in horses in Costa Rica].. Rev Latinoam Microbiol 1973 Apr-Jun;15(2):95-8.
    pubmed: 4519949
  13. León B, Käsbohrer A, Hutter SE, Baldi M, Firth CL, Romero-Zúñiga JJ, Jiménez C. National Seroprevalence and Risk Factors for Eastern Equine Encephalitis and Venezuelan Equine Encephalitis in Costa Rica.. J Equine Vet Sci 2020 Sep;92:103140.
    doi: 10.1016/j.jevs.2020.103140pubmed: 32797803google scholar: lookup
  14. León B, Jiménez C, González R, Ramirez-Carvajal L. First Complete Coding Sequence of a Venezuelan Equine Encephalitis Virus Strain Isolated from an Equine Encephalitis Case in Costa Rica.. Microbiol Resour Announc 2019 Sep 5;8(36).
    doi: 10.1128/MRA.00672-19pmc: PMC6728638pubmed: 31488528google scholar: lookup
  15. Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms.. Mol Biol Evol 2018 Jun 1;35(6):1547-1549.
    doi: 10.1093/molbev/msy096pmc: PMC5967553pubmed: 29722887google scholar: lookup
  16. Nguyen LT, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies.. Mol Biol Evol 2015 Jan;32(1):268-74.
    doi: 10.1093/molbev/msu300pmc: PMC4271533pubmed: 25371430google scholar: lookup
  17. Hoang DT, Chernomor O, von Haeseler A, Minh BQ, Vinh LS. UFBoot2: Improving the Ultrafast Bootstrap Approximation.. Mol Biol Evol 2018 Feb 1;35(2):518-522.
    doi: 10.1093/molbev/msx281pmc: PMC5850222pubmed: 29077904google scholar: lookup
  18. Miller MA, Pfeiffer W, Schwartz T. Creating the CIPRES Science Gateway for inference of large phylogenetic trees. Proceedings of the 2010 Gateway Computing Environments Workshop (GCE) New Orleans, LA, USA. 14 November 2010; Piscataway, NJ, USA: IEEE; 2010. pp. 1–8.
  19. Rambaut A, Lam TT, Max Carvalho L, Pybus OG. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen).. Virus Evol 2016 Jan;2(1):vew007.
    doi: 10.1093/ve/vew007pmc: PMC4989882pubmed: 27774300google scholar: lookup
  20. Martin DP, Murrell B, Golden M, Khoosal A, Muhire B. RDP4: Detection and analysis of recombination patterns in virus genomes.. Virus Evol 2015;1(1):vev003.
    doi: 10.1093/ve/vev003pmc: PMC5014473pubmed: 27774277google scholar: lookup
  21. Baele G, Lemey P, Bedford T, Rambaut A, Suchard MA, Alekseyenko AV. Improving the accuracy of demographic and molecular clock model comparison while accommodating phylogenetic uncertainty.. Mol Biol Evol 2012 Sep;29(9):2157-67.
    doi: 10.1093/molbev/mss084pmc: PMC3424409pubmed: 22403239google scholar: lookup
  22. Bouckaert R, Vaughan TG, Barido-Sottani J, Duchêne S, Fourment M, Gavryushkina A, Heled J, Jones G, Kühnert D, De Maio N, Matschiner M, Mendes FK, Müller NF, Ogilvie HA, du Plessis L, Popinga A, Rambaut A, Rasmussen D, Siveroni I, Suchard MA, Wu CH, Xie D, Zhang C, Stadler T, Drummond AJ. BEAST 2.5: An advanced software platform for Bayesian evolutionary analysis.. PLoS Comput Biol 2019 Apr;15(4):e1006650.
  23. Rambaut A, Drummond AJ, Xie D, Baele G, Suchard MA. Posterior Summarization in Bayesian Phylogenetics Using Tracer 1.7.. Syst Biol 2018 Sep 1;67(5):901-904.
    doi: 10.1093/sysbio/syy032pmc: PMC6101584pubmed: 29718447google scholar: lookup
  24. Drummond AJ, Rambaut A. BEAST: Bayesian evolutionary analysis by sampling trees.. BMC Evol Biol 2007 Nov 8;7:214.
    doi: 10.1186/1471-2148-7-214pmc: PMC2247476pubmed: 17996036google scholar: lookup
  25. Murrell B, Weaver S, Smith MD, Wertheim JO, Murrell S, Aylward A, Eren K, Pollner T, Martin DP, Smith DM, Scheffler K, Kosakovsky Pond SL. Gene-wide identification of episodic selection.. Mol Biol Evol 2015 May;32(5):1365-71.
    doi: 10.1093/molbev/msv035pmc: PMC4408417pubmed: 25701167google scholar: lookup
  26. Kosakovsky Pond SL, Frost SD. Not so different after all: a comparison of methods for detecting amino acid sites under selection.. Mol Biol Evol 2005 May;22(5):1208-22.
    doi: 10.1093/molbev/msi105pubmed: 15703242google scholar: lookup
  27. Smith MD, Wertheim JO, Weaver S, Murrell B, Scheffler K, Kosakovsky Pond SL. Less is more: an adaptive branch-site random effects model for efficient detection of episodic diversifying selection.. Mol Biol Evol 2015 May;32(5):1342-53.
    doi: 10.1093/molbev/msv022pmc: PMC4408413pubmed: 25697341google scholar: lookup
  28. Pond SL, Frost SD. Datamonkey: rapid detection of selective pressure on individual sites of codon alignments.. Bioinformatics 2005 May 15;21(10):2531-3.
    doi: 10.1093/bioinformatics/bti320pubmed: 15713735google scholar: lookup
  29. Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y. The I-TASSER Suite: protein structure and function prediction.. Nat Methods 2015 Jan;12(1):7-8.
    doi: 10.1038/nmeth.3213pmc: PMC4428668pubmed: 25549265google scholar: lookup
  30. Zhang R, Hryc CF, Cong Y, Liu X, Jakana J, Gorchakov R, Baker ML, Weaver SC, Chiu W. 4.4 Å cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus.. EMBO J 2011 Aug 9;30(18):3854-63.
    doi: 10.1038/emboj.2011.261pmc: PMC3173789pubmed: 21829169google scholar: lookup
  31. Schrödinger Release 2021-4: MacroModel. Schrödinger, LLC; New York, NY, USA: 2021.
  32. Pires DE, Ascher DB, Blundell TL. DUET: a server for predicting effects of mutations on protein stability using an integrated computational approach.. Nucleic Acids Res 2014 Jul;42(Web Server issue):W314-9.
    doi: 10.1093/nar/gku411pmc: PMC4086143pubmed: 24829462google scholar: lookup
  33. Lanfear R, Frandsen PB, Wright AM, Senfeld T, Calcott B. PartitionFinder 2: New Methods for Selecting Partitioned Models of Evolution for Molecular and Morphological Phylogenetic Analyses.. Mol Biol Evol 2017 Mar 1;34(3):772-773.
    doi: 10.1093/molbev/msw260pubmed: 28013191google scholar: lookup
  34. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool.. J Mol Biol 1990 Oct 5;215(3):403-10.
    doi: 10.1016/S0022-2836(05)80360-2pubmed: 2231712google scholar: lookup
  35. Goddard TD, Huang CC, Meng EC, Pettersen EF, Couch GS, Morris JH, Ferrin TE. UCSF ChimeraX: Meeting modern challenges in visualization and analysis.. Protein Sci 2018 Jan;27(1):14-25.
    doi: 10.1002/pro.3235pmc: PMC5734306pubmed: 28710774google scholar: lookup
  36. Oberste MS, Fraire M, Navarro R, Zepeda C, Zarate ML, Ludwig GV, Kondig JF, Weaver SC, Smith JF, Rico-Hesse R. Association of Venezuelan equine encephalitis virus subtype IE with two equine epizootics in Mexico.. Am J Trop Med Hyg 1998 Jul;59(1):100-7.
    doi: 10.4269/ajtmh.1998.59.100pubmed: 9684636google scholar: lookup
  37. Campillo-Sainz C. Incidencia de las infecciones por arbovirus eneefalitógenos en Méxieo. Rev. Salud Pública Mex. 1968;10:25–29.
  38. SCHERER WF, DICKERMAN RW, CHIA CW, VENTURA A, MOORHOUSE A, GEIGER R. VENEZUELAN EQUINE ENCEPHALITIS VIRUS IN VERACRUZ, MEXICO, AND THE USE OF HAMSTERS AS SENTINELS.. Science 1964 Jul 17;145(3629):274-5.
    doi: 10.1126/science.145.3629.274pubmed: 14171568google scholar: lookup
  39. Gonzalez-Salazar D, Estrada-Franco JG, Carrara AS, Aronson JF, Weaver SC. Equine amplification and virulence of subtype IE Venezuelan equine encephalitis viruses isolated during the 1993 and 1996 Mexican epizootics.. Emerg Infect Dis 2003 Feb;9(2):161-8.
    doi: 10.3201/eid0902.020124pmc: PMC2901937pubmed: 12603985google scholar: lookup
  40. Young NA, Johnson KM. Antigenic variants of Venezuelan equine encephalitis virus: their geographic distribution and epidemiologic significance.. Am J Epidemiol 1969 Mar;89(3):286-307.
  41. Brault AC, Powers AM, Ortiz D, Estrada-Franco JG, Navarro-Lopez R, Weaver SC. Venezuelan equine encephalitis emergence: enhanced vector infection from a single amino acid substitution in the envelope glycoprotein.. Proc Natl Acad Sci U S A 2004 Aug 3;101(31):11344-9.
    doi: 10.1073/pnas.0402905101pmc: PMC509205pubmed: 15277679google scholar: lookup
  42. 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.
  43. Brault AC, Powers AM, Weaver SC. Vector infection determinants of Venezuelan equine encephalitis virus reside within the E2 envelope glycoprotein.. J Virol 2002 Jun;76(12):6387-92.
  44. Varjak M, Zusinaite E, Merits A. Novel functions of the alphavirus nonstructural protein nsP3 C-terminal region.. J Virol 2010 Mar;84(5):2352-64.
    doi: 10.1128/JVI.01540-09pmc: PMC2820926pubmed: 20015978google scholar: lookup
  45. Foy NJ, Akhrymuk M, Shustov AV, Frolova EI, Frolov I. Hypervariable domain of nonstructural protein nsP3 of Venezuelan equine encephalitis virus determines cell-specific mode of virus replication.. J Virol 2013 Jul;87(13):7569-84.
    doi: 10.1128/JVI.00720-13pmc: PMC3700263pubmed: 23637407google scholar: lookup
  46. Oberste MS, Parker MD, Smith JF. Complete sequence of Venezuelan equine encephalitis virus subtype IE reveals conserved and hypervariable domains within the C terminus of nsP3.. Virology 1996 May 1;219(1):314-20.
    doi: 10.1006/viro.1996.0254pubmed: 8623548google scholar: lookup
  47. Kim DY, Atasheva S, Frolova EI, Frolov I. Venezuelan equine encephalitis virus nsP2 protein regulates packaging of the viral genome into infectious virions.. J Virol 2013 Apr;87(8):4202-13.
    doi: 10.1128/JVI.03142-12pmc: PMC3624340pubmed: 23365438google scholar: lookup
  48. Sharma A, Knollmann-Ritschel B. Current Understanding of the Molecular Basis of Venezuelan Equine Encephalitis Virus Pathogenesis and Vaccine Development.. Viruses 2019 Feb 18;11(2).
    doi: 10.3390/v11020164pmc: PMC6410161pubmed: 30781656google scholar: lookup
  49. Greene IP, Paessler S, Austgen L, Anishchenko M, Brault AC, Bowen RA, Weaver SC. Envelope glycoprotein mutations mediate equine amplification and virulence of epizootic venezuelan equine encephalitis virus.. J Virol 2005 Jul;79(14):9128-33.

Citations

This article has been cited 0 times.