Abstract
Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne alphavirus that has caused large outbreaks of severe illness in both horses and humans. New approaches are needed to rapidly infer the origin of a newly discovered VEEV strain, estimate its equine amplification and resultant epidemic potential, and predict human virulence phenotype. We performed whole genome single nucleotide polymorphism (SNP) analysis of all available VEE antigenic complex genomes, verified that a SNP-based phylogeny accurately captured the features of a phylogenetic tree based on multiple sequence alignment, and developed a high resolution genome-wide SNP microarray. We used the microarray to analyze a broad panel of VEEV isolates, found excellent concordance between array- and sequence-based SNP calls, genotyped unsequenced isolates, and placed them on a phylogeny with sequenced genomes. The microarray successfully genotyped VEEV directly from tissue samples of an infected mouse, bypassing the need for viral isolation, culture and genomic sequencing. Finally, we identified genomic variants associated with serotypes and host species, revealing a complex relationship between genotype and phenotype.
Highlights
Venezuelan equine encephalitis (VEE) virus (VEEV) is a mosquito-borne alphavirus capable of causing large outbreaks of encephalitis in humans and horses
We explored the relationship between genome variation and serotype, identified a number of variants non-randomly associated with these phenotypes, and examined the distribution of these variants across the Venezuelan equine encephalitis virus (VEEV) genome
We found that the single nucleotide polymorphism (SNP) tree built using maximum parsimony (Fig 1) was more similar to the multiple sequence alignment (MSA)-based tree than those built with neighbor joining (NJ) or maximum likelihood (ML)
Summary
Venezuelan equine encephalitis (VEE) virus (VEEV) is a mosquito-borne alphavirus capable of causing large outbreaks of encephalitis in humans and horses. VEE complex viruses are endemic to South and Central America, Mexico, and Florida [1]. The case-fatality rate of VEEV is low in human infections (usually less than 1%), infection is typically highly debilitating and sometimes results in permanent neurological sequelae [2]. Because the disease primarily occurs in isolated rural areas and typical infections initially present with nonspecific flu-like symptoms, many cases involving spillover from enzootic cycles go undiagnosed or are mistaken for other febrile diseases such as dengue [3]. Enzootic VEE is of concern due to its high burden of endemic human disease. For U.S war fighters engaged in a conflict in Latin America, either direct exposure to the enzootic cycle
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