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

Amanda Phelps,Lin Eastaugh,Jane Ennis,Mark Lever,Alejandro Nunez,Lyn O’Brien,David Ulaeto,Carwyn Davies,Larry Zeitlin

doi:10.3390/v9070163

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.

Highlights

Western equine encephalitis virus (WEEV) is a member of the alphavirus genus of the familyTogaviridae
Three independent experiments were undertaken to assess the viability of WEEV Fleming following aerosolisation in the AeroMP aerosol apparatus (Biaera Technologies, LLC, Hagerstown, MD, USA)
There was a linear relationship between data sets with a mean difference of 3.4 Log10 plaque forming with equivalent databetween produced using the closely alphavirus, when aerosolised units/mL

Summary

Introduction

Western equine encephalitis virus (WEEV) is a member of the alphavirus genus of the familyTogaviridae. Western equine encephalitis virus (WEEV) is a member of the alphavirus genus of the family. Alphaviruses, Venezuelan equine encephalitis virus (VEEV), Eastern equine encephalitis virus (EEEV), and WEEV are grouped geographically as New World viruses capable of causing disease in both equids and humans, exhibiting overt encephalitic features in a significant number of cases. WEEV causes periodic epizootic outbreaks in Western and Central North America and is maintained in an enzootic cycle between mosquitos and birds or rodents [1] Humans are usually infected as a result of close proximity to infected equines and by being bitten by an infected mosquito. WEEV infections are generally asymptomatic but may result in the onset of flu-like symptoms; fever, malaise, headaches, vomiting, and nausea. In a minority of cases, symptoms progress to weakness, confusion, seizures, and encephalitis, and may lead to coma and death.

Methods

Results

Conclusion