title: Virulence variation among isolates of western equine encephalitis virus in an outbred mouse model.
abstract: Little is known about viral determinants of virulence associated with western equine encephalitis virus (WEEV). Here, we have analysed six North American WEEV isolates in an outbred CD1 mouse model. Full genome sequence analyses showed < or =2.7 % divergence among the six WEEV isolates. However, the percentage mortality and mean time to death (MTD) varied significantly when mice received subcutaneous injections of 10(3) p.f.u. of each virus. Two WEEV strains, McMillan (McM) and Imperial 181 (IMP), were the most divergent of the six in genome sequence; McM caused 100 % mortality by 5 days post-infection, whereas IMP caused no mortality. McM had significantly higher titres in the brain than IMP. Similar differences in virulence were observed when McM and IMP were administered by aerosol, intranasal or intravenous routes. McM was 100 % lethal with an MTD of 1.9 days when 10(3) p.f.u. of each virus was administered by intracerebral inoculation; in contrast, IMP caused no mortality. The presence of IMP in the brains after infection by different routes and the lack of observed mortality confirmed that IMP is neuroinvasive but not neurovirulent. Based on morbidity, mortality, MTD, severity of brain lesions, virus distribution patterns, routes of infection and differences in infection of cultured cells, McM and IMP were identified as high- and low-virulence isolates, respectively.
authors.affiliation: Arthropod-Borne and Infectious Diseases Laboratory (AIDL), Colorado State University, Fort Collins, CO 80523, USA.|Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention (CDC), Fort Collins, CO 80521, USA.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Logue
authors.affiliation: Arthropod-Borne and Infectious Diseases Laboratory (AIDL), Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Bosio
authors.affiliation: Arthropod-Borne and Infectious Diseases Laboratory (AIDL), Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Welte
authors.affiliation: Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention (CDC), Fort Collins, CO 80521, USA.
authors.forename: Kimberley M
authors.initials: KM
authors.lastname: Keene
authors.affiliation: Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention (CDC), Fort Collins, CO 80521, USA.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Ledermann
authors.affiliation: Arthropod-Borne and Infectious Diseases Laboratory (AIDL), Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Phillips
authors.affiliation: Veterinary Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Sheahan
authors.affiliation: Arthropod-Borne and Infectious Diseases Laboratory (AIDL), Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Pierro
authors.affiliation: Arthropod-Borne and Infectious Diseases Laboratory (AIDL), Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Marlenee
authors.affiliation: Center for Vector-Borne Diseases, University of California, Davis, CA, USA.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Brault
authors.affiliation: Arthropod-Borne and Infectious Diseases Laboratory (AIDL), Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Catharine M
authors.initials: CM
authors.lastname: Bosio
authors.affiliation: Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention (CDC), Fort Collins, CO 80521, USA.
authors.forename: Amber J
authors.initials: AJ
authors.lastname: Singh
authors.affiliation: Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention (CDC), Fort Collins, CO 80521, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Powers
authors.affiliation: Arthropod-Borne and Infectious Diseases Laboratory (AIDL), Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Ken E
authors.initials: KE
authors.lastname: Olson
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D016000:Cluster Analysis; D004667:Encephalitis Virus, Western Equine / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity*; D004683:Encephalomyelitis, Equine / Q000821:virology*; D014644:Genetic Variation; D016679:Genome, Viral; D006651:Histocytochemistry / Q000379:methods; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D016019:Survival Analysis; D010948:Viral Plaque Assay / Q000379:methods; D014774:Virulence
chemical_list: D012367:RNA, Viral