Pathogenesis of aerosolized Eastern Equine Encephalitis virus infection in guinea pigs

Area of Science:

• Veterinary Virology
• Neuroscience
• Infectious Diseases

Background:

• Eastern equine encephalitis virus (EEEV) is a significant public health threat.
• Understanding EEEV transmission and pathogenesis is crucial for developing effective countermeasures.
• Aerosol exposure is a relevant route for EEEV infection, mimicking natural transmission.

Purpose of the Study:

• To evaluate guinea pigs as an animal model for aerosolized EEEV infection.
• To compare the susceptibility and clinical manifestations of EEEV infection in mice and guinea pigs.
• To elucidate the neuroinvasive pathway of aerosolized EEEV in a mammalian model.

Main Methods:

• Experimental exposure of mice and guinea pigs to aerosolized EEEV (strains NJ1959 or ArgM) at different particle sizes.
• Assessment of clinical signs, lethality (LD50), virus isolation, and immunohistochemistry.
• Histopathological examination of brain tissues to identify viral targets and lesions.

Main Results:

• Guinea pigs exhibited more pronounced encephalitis signs than mice, despite lower overall susceptibility.
• Neuroinvasion occurred within one day postexposure in guinea pigs, primarily through the olfactory system.
• EEEV targeted olfactory neurons and spread transneuronally throughout the brain, causing neuronal necrosis, inflammation, and vasculitis.

Conclusions:

• Guinea pigs serve as a suitable animal model for studying aerosolized EEEV infection, recapitulating key features of human disease.
• The olfactory system is a critical route for EEEV neuroinvasion following aerosol exposure.
• Further research using this model can advance understanding of EEEV pathogenesis and inform therapeutic strategies.