Venezuelan equine encephalitis in BALB/c mice: kinetic analysis of central nervous system infection following aerosol or subcutaneous inoculation.

OBJECTIVE

To investigate the routes of entry of Venezuelan equine encephalitis (VEE) virus into the brain, we infected BALB/c mice with a virulent strain (V3000) by aerosol or subcutaneous inoculation.

METHODS

Immunohistochemistry and in situ hybridization methods were used to detect VEE virus in tissues taken at daily intervals postinfection.

RESULTS

In both groups, virus in the brain first appeared in olfactory regions. Aerosol exposure caused early massive infection of olfactory epithelium, which developed into bilaterally symmetrical infection of the olfactory nerves, olfactory bulbs, and lateral olfactory tracts by day 2 postinfection. After subcutaneous inoculation, VEE in the brain also appeared first in olfactory regions, but was not detected until day 3 postinfection. By day 4 postinfection, VEE viral infection had spread throughout the brain in both groups. Vascular endothelium and the choroid plexus remained uninfected during the entire study.

CONCLUSIONS

Our findings suggest that VEE virus, whether given by aerosol or subcutaneously, first enters the brain through the olfactory tract.