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Viruses 2017, 9(7), 163; doi:10.3390/v9070163

Susceptibility and Lethality of Western Equine Encephalitis Virus in Balb/c Mice When Infected by the Aerosol Route

1
CBR Division, Defence Science and Technology Laboratory (Dstl), Room 201, Building 7a, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK
2
Mapp Biopharmaceutical Inc., 6160 Lusk Blvd. #C105, San Diego, CA 92121, USA
3
Pathology Department, Animal and Plant Health Agency, Weybrige, Woodham Lane, New Haw, Addlestone, Surrey, KT15 3NB, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 8 May 2017 / Revised: 9 June 2017 / Accepted: 20 June 2017 / Published: 27 June 2017
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [1738 KB, uploaded 28 June 2017]   |  

Abstract

Western equine encephalitis virus (WEEV) naturally cycles between mosquitos and birds or rodents, with a case fatality rate of up to 15% in humans during epizootic outbreaks. There are no medical countermeasures to treat WEEV infection, and accidental aerosol exposure increases the case fatality rate up to 40%. Understanding the pathogenesis of infection is required to develop and assess medical countermeasures. This study describes the clinical and pathological findings of mice infected with WEEV by the aerosol route, and use as a model for WEEV infection in humans. Balb/c mice were infected by the aerosol route with a dose range of high-virulence WEEV strain Fleming to establish the median lethal dose (MLD). The disease course was acute, culminating in severe clinical signs, neuroinvasion, and dose-dependent mortality. Further groups of mice were exposed by the aerosol route, periodically sacrificed, and tissues excised for histopathological examination and virology. Viral titres peaked four days post-challenge in the brain and lungs, corresponding with severe bilateral lesions in rostroventral regions of the encephalon, especially in the olfactory bulb and piriform cortex. Recapitulation of the most serious clinical presentations of human WEEV disease in mice may prove a useful tool in the evaluation of medical countermeasures. View Full-Text
Keywords: alphavirus; western equine encephalitis virus; WEEV; pathogenicity; median lethal dose (MLD); mouse; aerosol alphavirus; western equine encephalitis virus; WEEV; pathogenicity; median lethal dose (MLD); mouse; aerosol
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Phelps, A.L.; O’Brien, L.M.; Eastaugh, L.S.; Davies, C.; Lever, M.S.; Ennis, J.; Zeitlin, L.; Nunez, A.; Ulaeto, D.O. Susceptibility and Lethality of Western Equine Encephalitis Virus in Balb/c Mice When Infected by the Aerosol Route. Viruses 2017, 9, 163.

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