Pathogenesis of Aerosolized Eastern Equine Encephalitis Virus Infection in Guinea Pigs
Abstract
Mice and guinea pigs were exposed to aerosols containing either the NJ1959 or ArgM strains of Eastern Equine Encephalitis virus (EEEV). Mice were more susceptible to either strain of aerosolized EEEV than were guinea pigs; however, clinical signs indicative of encephalitis were more readily seen in guinea pigs. Lethality was lower for EEEV at large aerosol particle sizes (>3 m) although the differences in the median lethal dose (LD50) were not statistically significant. Virus isolation and immunohistochemistry indicated that virus invaded the brains of guinea pigs within one day of aerosol exposure, regardless of virus strain or particle size. Immunohistochemistry further demonstrated that neuroinvasion occurred via the olfactory system, followed by transneuronal spread to all regions of the brain. Olfactory bipolar neurons and neurons throughout the brain were the key viral targets. The main microscopic lesions in infected guinea pigs were neuronal necrosis, inflammation of the meninges and neuropil of the brain and vasculitis in the brain. These results indicate that guinea pigs infected by aerosolized EEEV recapitulate several key features of fatal human infection and thus should serve as a suitable animal model for aerosol exposure to EEEV.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2009
- Accession Number
- ADA513299
Entities
People
- Catherine L. Wilhelmsen
- Chad J Roy
- Douglas S. Reed
- Justin Hartings
- Keith E. Steele
- Sarah L. Norris
Organizations
- United States Army Medical Research Institute of Infectious Diseases