The Earliest Events in Vesicular Stomatitis Virus Infection of the Murine Olfactory Neuroepithelium and Entry of the Central Nervous System

After intranasal instillation of mice with vesicular stomatitis virus (VSV), olfactory receptor neurons are infected. By 12 to 24 hr postinfection, VSV antigens are observed in adjoining supporting and basal cells and in other structures of the olfactory epithelium and lamina propria. Peripheral deafferentation of the olfactory epithelium with Triton X-100 or bilateral surgical bulbectomy does not prevent spread of VSV to the central nervous system (CNS); the route of spread differs considerably from the route taken when the olfactory nerve is intact. In contrast to rabies virus and HSV-1, VSV does not use the trigeminal nerve for entry into the brain, as the trigeminal ganglion remains virus-free following intranasal infection. These results indicate that VSV has a strong tropism for olfactory receptor cells, using them for entry into the CNS. Both retrograde and anterograde transneuronal and nonneuronal (ependymal cells and cerebrospinal fluid) pathways are utilized by VSV within the CNS.