Virulence variation among isolates of western equine encephalitis virus in an outbred mouse model

• Published in: Journal of general virology Vol. 90; no. 8; pp. 1848 - 1858
• Main Authors: Logue, Christopher H, Bosio, Christopher F, Welte, Thomas, Keene, Kimberley M, Ledermann, Jeremy P, Phillips, Aaron, Sheahan, Brian J, Pierro, Dennis J, Marlenee, Nicole, Brault, Aaron C, Bosio, Catharine M, Singh, Amber J, Powers, Ann M, Olson, Ken E
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.08.2009; Society for General Microbiology
• Subjects: Animal; Animals; Biological and medical sciences; Brain - pathology; Brain - virology; Cluster Analysis; Encephalitis Virus, Western Equine - genetics; Encephalitis Virus, Western Equine - isolation & purification; Encephalitis Virus, Western Equine - pathogenicity; Encephalomyelitis, Equine - virology; Fundamental and applied biological sciences. Psychology; Genetic Variation; genome; Genome, Viral; Histocytochemistry - methods; Mice; Microbiology; Miscellaneous; Molecular Sequence Data; mortality; nucleotide sequences; Phylogeny; RNA, Viral - genetics; Sequence Analysis, DNA; Sequence Homology; strain differences; Survival Analysis; viral encephalitis; Viral Plaque Assay - methods; Virology; Virulence; Western equine encephalitis virus; Virus; Animal model; Microbiology; Virulence; Togaviridae; Alphavirus; Isolate; Veterinary; Western equine encephalomyelitis virus
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.008656-0

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 10³ 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 10³ 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.