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Pathology of Animal Models of Alphavirus Encephalitis

pathvet

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China Veterinary Student
Pathology of Animal Models of Alphavirus Encephalitis
by K. E. Steele and N. A. Twenhafel
Veterinary Pathology, 2010, 47(5): 790-805
Abstract:
The encephalitides caused by Venezuelan (VEEV), eastern (EEEV), and western (WEEV) equine encephalitis viruses are important
natural diseases of horses and humans and potential agents of biowarfare or bioterrorism. No licensed vaccines or specific
therapies exist to prevent or treat human infections with VEEV, EEEV, or WEEV. Well-characterized animal models are needed
to support the development of such medical countermeasures under the United States Food and Drug Administration’s ‘‘Animal
Rule.’’ This review focuses on the pathological features and pathogenetic mechanisms of these alphaviral encephalitides in animal
models, with an emphasis on aerosol infections. Infection of mice, nonhuman primates, and other species with VEEV, EEEV, and
WEEV causes encephalitis and often death. There is great variability in the specific manifestations of disease in the different models,
however. Many aspects of the disease in animal models and in humans remain to be characterized using modern methods.
Especially needed is a better understanding of the fundamental mechanisms involved in 3 key phases of the pathogenesis of alphavirus
encephalitis. These are the early extraneural phase, the process of neuroinvasion itself, and virus and host factors related to
neurovirulence. A greater understanding of these aspects could provide avenues for the development of medical countermeasures
and better establish suitable animal models of alphavirus encephalitis for testing them under the Animal Rule.
 
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