Virulence and viremia characteristics of 1992 epizootic subtype IC Venezuelan equine encephalitis viruses and closely related enzootic subtype ID strains

Following a 19-year hiatus, Venezuelan equine encephalitis (VEE) reemerged in western Venezuela in December 1992. This outbreak is important in unders tanding VEE emergence because phylogenetic studies imply that sympatric, en zootic, subtype ID VEE viruses mutated to generate the epizootic/epidemic. Although the 1992-1993 strains belong to subtype IC, a serotype implicated in extensive outbreaks during the 1960s and in 1995, relatively small numbe rs of human and equine cases occurred in 1992-1993. We, therefore, evaluate d the pathogenicity of these Venezuelan enzootic ID and epizootic IC viruse s to determine 1) if they exhibit phenotypes like those described previousl y for more distantly related enzootic and epizootic strains. and 2) if the 1992-1993 outbreak was limited by the inability of these IC viruses to expl oit equines as amplification hosts. All strains were virulent in mice and g uinea pigs, but were benign for cotton rats, natural hosts of enzootic viru ses. However, only the IC strains produced equine disease, with mean peak v iremias of 10(5) suckling mouse 50% lethal doses per mL serum, and some tit ers exceeding 10(7). These viremias approximate those observed previously w ith VEE strains isolated during more extensive epizootics, suggesting that efficient equine amplification did not limit the scope and duration of the 1992-1993 outbreak. Enzootic ID virus infection protected all horses from c hallenge with epizootic strain P676, supporting the hypothesis that epizoot ics bypass regions of enzootic transmission due to natural immunization of equines by enzootic VEE viruses.