Sequencing of prototype viruses in the Venezuelan equine encephalitis antigenic complex

The 5' nontranslated region (5'NTR) and nonstructural region nucleotide seq uences of nine enzootic Venezuelan equine encephalitis (VEE) virus strains were determined, thus completing the genomic RNA sequences of all prototype strains. The full-length genomes, representing VEE virus antigenic subtype s I-VI, range in size from 11.3 to 11.5 kilobases, with 48-53% overall G C contents. Size disparities result from subtype-related differences in the number and length of direct repeats in the C-terminal nonstructural protei n 3 (nsP3) domain coding sequence and the 3'NTR, while G + C content dispar ities are attributable to strain-specific variations in base composition at the wobble position of the polyprotein codons. Highly-conserved protein co mponents and one nonconserved protein domain constitute the VEE virus repli case polyproteins. Approximately 80% of deduced nsP1 and nsP4 amino acid re sidues are invariant, compared to less than 20% of C-terminal nsP3 domain r esidues. In two enzootic strains, C-terminal nsP3 domain sequences degenera te into little more than repetitive serine-rich blocks. Nonstructural regio n sequence information drawn from a cross-section of VEE virus subtypes cla rifies features of alphavirus conserved sequence elements and proteinase re cognition signals. As well, whole-genome comparative analysis supports the reclassification of VEE subtype-variety IF and subtype II viruses. (C) 1999 Elsevier Science B.V. All rights reserved.