Envelope glycoprotein mutations mediate equine amplification and virulence of epizootic Venezuelan equine encephalitis virus

Ivorlyne P. Greene, Slobodan Paessler, Laura Austgen, Michael Anishchenko, Aaron C. Brault, Richard A. Bowen, Scott Weaver

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Epidemics of Venezuelan equine encephalitis (VEE) result from high-liter equine viremia of IAB and IC subtype viruses that mediate increased mosquito transmission and spillover to humans. Previous genetic studies suggest that mutations in the E2 envelope glycoprotein allow relatively viremia-incompetent, enzootic subtype ID strains to adapt for equine replication, leading to VEE emergence. To test this hypothesis directly, chimeric VEEV strains containing the genetic backbone of enzootic subtype ID strains and the partial envelope glycoprotein genes of epizootic subtype IC and IAB strains, as well as reciprocal chimeras, were used for experimental infections of horses. Insertion of envelope genes from two different, closely related enzootic subtype ID strains into the epizootic backbones resulted in attenuation, demonstrating that the epizootic envelope genes are necessary for the equine-virulent and viremia-competent phenotypes. The partial epizootic envelope genes introduced into an enzootic ID backbone were sufficient to generate the virulent, viremia-competent equine phenotype. These results indicate that a small number of envelope gene mutations can generate an equine amplification-competent, epizootic VEEV from an enzootic progenitor and underscore the limitations of small animal models for evaluating and predicting the epizootic phenotype.

Original languageEnglish (US)
Pages (from-to)9128-9133
Number of pages6
JournalJournal of Virology
Volume79
Issue number14
DOIs
StatePublished - Jul 2005

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Venezuelan Equine Encephalitis Viruses
Venezuelan equine encephalitis virus
Horses
Virulence
glycoproteins
Glycoproteins
virulence
Viremia
mutation
horses
Mutation
viremia
Venezuelan Equine Encephalomyelitides
Phenotype
Genes
encephalitis
genes
phenotype
Insertional Mutagenesis
Culicidae

ASJC Scopus subject areas

  • Immunology

Cite this

Envelope glycoprotein mutations mediate equine amplification and virulence of epizootic Venezuelan equine encephalitis virus. / Greene, Ivorlyne P.; Paessler, Slobodan; Austgen, Laura; Anishchenko, Michael; Brault, Aaron C.; Bowen, Richard A.; Weaver, Scott.

In: Journal of Virology, Vol. 79, No. 14, 07.2005, p. 9128-9133.

Research output: Contribution to journalArticle

Greene, Ivorlyne P. ; Paessler, Slobodan ; Austgen, Laura ; Anishchenko, Michael ; Brault, Aaron C. ; Bowen, Richard A. ; Weaver, Scott. / Envelope glycoprotein mutations mediate equine amplification and virulence of epizootic Venezuelan equine encephalitis virus. In: Journal of Virology. 2005 ; Vol. 79, No. 14. pp. 9128-9133.
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