2 NEUROTROPIC VIRUSES, HERPES-SIMPLEX VIRUS TYPE-1 AND MOUSE HEPATITIS-VIRUS, SPREAD ALONG DIFFERENT NEURAL PATHWAYS FROM THE MAIN OLFACTORY-BULB

Several neurotropic viruses enter the brain after peripheral inoculati on and spread transneuronally along pathways known to be connected to the initial site of entry. In this study, the pathways utilized by two such viruses, herpes simplex virus type 1 and mouse hepatitis virus s train JHM, were compared using in situ hybridization following inocula tion into either the nasal cavity or the main olfactory bulb of the mo use. The results indicate that both viruses spread to infect a unique and only partially overlapping set of connections of the main olfactor y bulb. Both quantitative and qualitative differences were observed in the patterns of infection of known primary and secondary main olfacto ry bulb connections. Using immunohistochemistry for tyrosine hydroxyla se combined with in situ hybridization, it was shown that only herpes simplex virus infected noradrenergic neurons in the locus coeruleus. I n contrast, both viruses infected dopaminergic neurons in the ventral tegmental area, although mouse hepatitis virus produced a more widespr ead infection in the A10 group, as well as infecting A8 and A9. The re sults suggest that differential virus uptake in specific neurotransmit ter systems contributes to the pattern of viral spread, although other factors, such as differences in access to particular synapses on infe cted cells and differences in the distribution of the cellular recepto r for the two viruses, are also likely to be important. The data show that neural tracing with different viruses may define unique neural pa thways from a site of inoculation. The data also demonstrate that two viruses can enter the brain via the olfactory system and localize to d ifferent structures, suggesting that neurological diseases involving d isparate regions of the brain could be caused by different viruses, ev en if entry occurred at a common site.