Genetic determinants of Venezuelan equine encephalitis emergence.

Following a period of inactivity from 1973-1991, Venezuelan equine encephalitis (VEE) reemerged during the past decade in South America and Mexico. Experimental studies of VEE virus (VEEV) infection of horses with virus strains isolated during these outbreaks have revealed considerable variation in the ability of equine-virulent, epizootic strains to exploit horses as efficient amplification hosts. Subtype IC strains from recent outbreaks in Venezuela and Colombia amplify efficiently in equines, with a correlation between maximum viremia titers and the extent of the outbreak from which the virus strain was isolated. Studies of enzootic VEEV strains that are believed to represent progenitors of the epizootic subtypes support the hypothesis that adaptation to efficient replication in equines is a major determinant of emergence and the ability of VEEV to spread geographically. Correlations between the ability of enzootic and epizootic VEEV strains to infect abundant, equiphilic mosquitoes, and the location and extent of these outbreaks, also suggest that specific adaptation to Ochlerotatus taeniorhynchus mosquitoes is a determinant of some but not all emergence events. Genetic studies imply that mutations in the E2 envelope glycoprotein gene are major determinants of adaptation to both equines and mosquito vectors.