Genetic evidence for the origins of Venezuelan equine encephalitis virus subtype IAB outbreaks

Epizootics of Venezuelan equine encephalitis (VEE) involving subtype IAB vi ruses occurred sporadically in South, Central and North America from 1938 t o 1973, Incompletely inactivated vaccines have long been suspected as a sou rce of the later epizootics. We tested this hypothesis by sequencing the PE 2 glycoprotein precursor (1,677 nucleotides) or 26S/nonstructural protein 4 (nsP4) genome regions (4,490 nucleotides) for isolates representing most m ajor outbreaks. Two distinct IAB genotypes were identified: 1) 1940s Peruvi an strains and 2) 1938-1973 isolates from South, Central, and North America . Nucleotide sequences of these two genotypes differed by 1.1%, while the l atter group showed only 0.6% sequence diversity. Early VEE virus IAB strain s that were used for inactivated vaccine preparation had sequences identica l to those predicted by phylogenetic analyses to be ancestors of the 1960s- 1970s outbreaks. These data support the hypothesis of a vaccine origin for many VEE outbreaks. However, continuous, cryptic circulation of IAB viruses cannot be ruled out as a source of epizootic emergence.