Non-lethal infection of aminergic reticular core neurons: age-dependent spread of ts mutant vesicular stomatitis virus from the nose.

In order to induce a non-lethal infection restricted to central aminergic neurons projecting to the olfactory bulbs a series of temperature sensitive (ts) and G-protein monoclonal antibody escape mutants of vesicular stomatitis virus (VSV) were instilled into the nasal cavity of mice. In three-week (wk)-old NMRI mice four monoclonal antibody escape mutants caused an extensive infection of the olfactory epithelium and, like a wild type strain, a lethal brain infection after spread along olfactory pathways. Three ts mutant strains showed an attenuated pathogenic potential. Strain G31 caused a lethal infection with a somewhat prolonged course while the strain G11 failed to invade the nervous system. Strain G41 showed minimal invasion of central nervous system in three-wk-old mice and caused a lethal infection in newborn and one-wk-old mice. In contrast, two-wk-old mice survived infection with this mutant, which spread along olfactory pathways and rather selectively affected aminergic reticular core neurons in the diagonal band, the locus ceruleus and the raphe nuclei in the brainstem. Thus, an age-dependent virus infection of the olfactory pathways can cause restricted lesions in the brain providing a model for studies of virus-induced changes in aminergic neurotransmission.