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Journal of Virology, May 1999, p. 4266-4271, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Genetic and Phenotypic Changes Accompanying the Emergence of Epizootic Subtype IC Venezuelan Equine Encephalitis Viruses from an Enzootic Subtype ID Progenitor

Eryu Wang,1 Roberto Barrera,2 Jorge Boshell,3 Cristina Ferro,3 Jerome E. Freier,4 Juan Carlos Navarro,2 Rosalba Salas,5 Clovis Vasquez,5 and Scott C. Weaver1,*

Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-06091; Instituto de Zoologia Tropical, Universidad Central de Venezuela,2 and Instituto Nacional de Higiene,5 Caracas, Venezuela; Instituto Nacional de Salud, Bogota, Colombia3; and USDA Center for Animal Disease Information and Analysis, Fort Collins, Colorado 805214

Received 29 October 1998/Accepted 26 January 1999

Recent studies have indicated that epizootic Venezuelan equine encephalitis (VEE) viruses can evolve from enzootic, subtype ID strains that circulate continuously in lowland tropical forests (A. M. Powers, M. S. Oberste, A. C. Brault, R. Rico-Hesse, S. M. Schmura, J. F. Smith, W. Kang, W. P. Sweeney, and S. C. Weaver, J. Virol. 71:6697-6705, 1997). To identify mutations associated with the phenotypic changes leading to epizootics, we sequenced the entire genomes of two subtype IC epizootic VEE virus strains isolated during a 1992-1993 Venezuelan outbreak and four sympatric, subtype ID enzootic strains closely related to the predicted epizootic progenitor. Analysis by maximum-parsimony phylogenetic methods revealed 25 nucleotide differences which were predicted to have accompanied the 1992 epizootic emergence; 7 of these encoded amino acid changes in the nsP1, nsP3, capsid, and E2 envelope glycoprotein, and 2 were mutations in the 3' untranslated genome region. Comparisons with the genomic sequences of IAB and other IC epizootic VEE virus strains revealed that only one of the seven amino acid changes associated with the 1992 emergence, a threonine-to-methionine change at position 360 of the nsP3 protein, accompanied another VEE virus emergence event. Two changes in the E2 envelope glycoprotein region believed to include the major antigenic determinants, both involving replacement of uncharged residues with arginine, are also candidates for epizootic determinants.


* Corresponding author. Mailing address: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609. Phone: (409) 747-0758. Fax: (409) 747-2415. E-mail: sweaver{at}utmb.edu.


Journal of Virology, May 1999, p. 4266-4271, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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