Herpes simplex encephalitis. Immunohistological demonstration of spread of virus via olfactory pathways in mice.

Six-week-old Balb/c mice were inoculated intranasally with a suspension of HSV1 virus and the distribution of viral antigen in the brain 3-7 days later was surveyed using the immunoperoxidase technique. Virus was first detectable in the brain 4 days later at 2 distinct sites: the trigeminal root entry zone in the brain stem and the olfactory bulbs. On succeeding days virus spread from the trigeminal focus to many other brain stem nuclei and, in some mice, to the thalamus and the cerebellum. From the olfactory bulbs, in a proportion of mice, virus spread to anterior olfactory nucleus, lateral olfactory tract, septal nuclei, temporal lobe, hippocampus and cingulate cortex. Infection of olfactory bulbs was found to occur following intracorneal as well as intranasal inoculation of virus. The relevance of this model to human herpes simplex encephalitis is discussed.