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

Christopher H. Logue, Christopher F. Bosio, Thomas Welte, Kimberley M. Keene, Jeremy P. Ledermann, Aaron Phillips, Brian J. Sheahan, Dennis J. Pierro, Nicole Marlenee, Aaron Brault, Catharine M. Bosio, Amber J. Singh, Ann M. Powers, Ken E. Olson

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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 ≤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.

Original languageEnglish (US)
Pages (from-to)1848-1858
Number of pages11
JournalJournal of General Virology
Volume90
Issue number8
DOIs
StatePublished - Oct 8 2009

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ASJC Scopus subject areas

  • Virology

Cite this

Logue, C. H., Bosio, C. F., Welte, T., Keene, K. M., Ledermann, J. P., Phillips, A., Sheahan, B. J., Pierro, D. J., Marlenee, N., Brault, A., Bosio, C. M., Singh, A. J., Powers, A. M., & Olson, K. E. (2009). Virulence variation among isolates of western equine encephalitis virus in an outbred mouse model. Journal of General Virology, 90(8), 1848-1858. https://doi.org/10.1099/vir.0.008656-0