RECOMBINATIONAL HISTORY AND MOLECULAR EVOLUTION OF WESTERN EQUINE ENCEPHALOMYELITIS COMPLEX ALPHAVIRUSES

Western equine encephalomyelitis (WEE) virus (Togaviridae: Alphavirus) was shown previously to have arisen by recombination between eastern equine encephalomyelitis (EEE)- and Sindbis-like viruses (C. S. Hahn, S. Lustig, E. G. Strauss, and J. H. Strauss, Proc. Natl. Acad. Sci. US A 85:5997-6001, 1988). We have now examined the recombinational histor y and evolution of all viruses belonging to the WEE antigenic complex, including the Buggy Creek, Fort Morgan, Highlands J, Sindbis, Babanki , Ockelbo, Kyzylagach, Whataroa, and Aura viruses, using nucleotide se quences derived from representative strains. Two regions of the genome were examined: sequences of 477 nucleotides from the C terminus of th e E1 envelope glycoprotein gene which in WEE virus was derived from th e Sindbis-like virus parent, and 517 nucleotide sequences at the C ter minus of the nsP4 gene which in WEE virus was derived from the EEE-lik e virus parent. Trees based on the El region indicated that all member s of the WEE virus complex comprise a monophyletic group. Most closely related to WEE viruses are other New World members of the complex: th e Highlands J, Buggy Creek, and Fort Morgan viruses. More distantly re lated WEE complex viruses included the Old World Sindbis, Babanki, Ock elbo, Kyzylagach, and Whataroa viruses, as well as the New World Aura virus. Detailed analyses of 38 strains of WEE virus revealed at least 4 major lineages; two were represented by isolates from Argentina, one was from Brazil, and a fourth contained isolates from many locations in South and North America as well as Cuba. Trees based on the nsP4 ge ne indicated that all New World WEE complex viruses except Aura virus are recombinants derived from EEE- and Sindbis-like virus ancestors. I n contrast, the Old World members of the WEE complex, as well as Aura virus, did not appear to have recombinant genomes. Using an evolutiona ry rate estimate (2.8 x 10(-4) substitutions per nucleotide per year) obtained from E1-3' sequences of WEE viruses, we estimated that the re combination event occurred in the New World 1,300 to 1,900 years ago. This suggests that the alphaviruses originated in the New World a few thousand years ago.