title: Characterization of Genetic Variability of Venezuelan Equine Encephalitis Viruses.
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.
authors.affiliation: Computations, Lawrence Livermore National Laboratory, Livermore, California, United States of America.
authors.forename: Shea N
authors.initials: SN
authors.lastname: Gardner
authors.affiliation: Computations, Lawrence Livermore National Laboratory, Livermore, California, United States of America.
authors.forename: Kevin
authors.initials: K
authors.lastname: McLoughlin
authors.affiliation: Physical and Life Sciences, Lawrence Livermore National Laboratory, Livermore, California, United States of America.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Be
authors.affiliation: Computations, Lawrence Livermore National Laboratory, Livermore, California, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Allen
authors.affiliation: Institute for Human Infections and Immunity and Departments of Microbiology & Immunology and Pathology, University of Texas, Medical Branch, Galveston, Texas, United States of America.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
authors.affiliation: Institute for Human Infections and Immunity and Departments of Microbiology & Immunology and Pathology, University of Texas, Medical Branch, Galveston, Texas, United States of America.
authors.forename: Naomi
authors.initials: N
authors.lastname: Forrester
authors.affiliation: Institute for Human Infections and Immunity and Departments of Microbiology & Immunology and Pathology, University of Texas, Medical Branch, Galveston, Texas, United States of America.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Guerbois
authors.affiliation: Physical and Life Sciences, Lawrence Livermore National Laboratory, Livermore, California, United States of America.
authors.forename: Crystal
authors.initials: C
authors.lastname: Jaing
mesh_terms: D000818:Animals; D006224:Cricetinae / Q000821:virology; D009033:Culicidae / Q000821:virology; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics* / Q000302:isolation & purification; D004685:Encephalomyelitis, Venezuelan Equine / Q000453:epidemiology; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D054884:Host-Pathogen Interactions / Q000235:genetics; D008800:Mexico / Q000453:epidemiology; D008815:Mice, Inbred Strains / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010641:Phenotype; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide