The use of chimeric Venezuelan equine encephalitis viruses as an approach for the molecular identification of natural virulence determinants

Ann M. Powers, Aaron C. Brault, Richard M. Kinney, Scott Weaver

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Abstract

Venezuelan equine encephalitis (VEE) virus antigenic subtypes and varieties are considered either epidemic/epizootic or enzootic. In addition to epidemiological differences between the epidemic and enzootic viruses, several in vitro and in vivo laboratory markers distinguishing the viruses have been identified, including differential plaque size, sensitivity to interferon (IFN), and virulence for guinea pigs. These observations have been shown to be useful predictors of natural, equine virulence and epizootic potential. Chimeric viruses containing variety IAB (epizootic) nonstructural genes with variety IE (enzootic) structural genes (VE/IAB-IE) or IE nonstructural genes and IAB structural genes (IE/IAB) were constructed to systematically analyze and map viral phenotype and virulence determinants. Plaque size analysis showed that both chimeric viruses produced a mean plaque diameter that was intermediate between those of the parental strains. Additionally, both chimeric viruses showed intermediate levels of virus replication and virulence for guinea pigs compared to the parental strains. However, IE/IAB produced a slightly higher viremia and an average survival time 2 days shorter than the VE/IAB-IE virus. Finally, IFN sensitivity assays revealed that only one chimera, VE/IAB-IE, was intermediate between the two parental types. The second chimera, containing the IE nonstructural genes, was at least five times more sensitive to IFN than the IE parental virus and greater than 50 times more sensitive than the IAB parent. These results implicate viral components in both the structural and nonstructural portions of the genome in contributing to the epizootic phenotype and indicate the potential for epidemic emergence from the IE enzootic VEE viruses.

Original languageEnglish (US)
Pages (from-to)4258-4263
Number of pages6
JournalJournal of Virology
Volume74
Issue number9
DOIs
StatePublished - 2000

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Venezuelan Equine Encephalitis Viruses
Venezuelan equine encephalitis virus
Virulence
virulence
Viruses
viruses
interferons
Interferons
structural genes
Genes
chimerism
guinea pigs
Guinea Pigs
Phenotype
phenotype
Viral Structures
genes
Viremia
viremia
Virus Replication

ASJC Scopus subject areas

  • Immunology

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The use of chimeric Venezuelan equine encephalitis viruses as an approach for the molecular identification of natural virulence determinants. / Powers, Ann M.; Brault, Aaron C.; Kinney, Richard M.; Weaver, Scott.

In: Journal of Virology, Vol. 74, No. 9, 2000, p. 4258-4263.

Research output: Contribution to journalArticle

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