This project investigates neural regenerative responses to infection in a herpesvirus model, with comparisons to regenerative responses observed in classical axotomy models. Initial studies examine the effects of herpes simplex virus type-2 (HSV-2) infection on host dorsal root ganglia (DRG) in a mouse sensory ganglia/spinal cord model. During FY 1991, the following issues were addressed: 1) Do specific subpopulations of DRG neurons, as characterized by morphology, connections and neuropeptide content, become infected following HSV-2 inoculation and later harbor latent virus, and 2) Does the progression of HSV-2 infection alter normal neuropeptide production in the host ganglia. Major findings are: 1) Route of inoculation plays an important role in determining which populations of DRG neurons are acutely infected. Peripheral inoculation establishes HSV-2 infection in the small subpopulation, muscle inoculation tends to spare the smallest neurons while infecting medium- and large-size cells, and intraneural inoculation, by two different methods, targets the entire spectrum of cell sizes. These results suggest that the virus does not show selectivity for a particular neuronal subpopulation and that infection is determined by the accessibility of the neuronal processes to virus. 2) There is selective modulation of host cell neuropeptide production during the course of HSV-2 infection. Galanin, normally undetectable in adult DRG neurons, is selectively expressed 2 wks following viral infection, the neuropeptide calcitonin gene-related peptide does not appear affected, and the number of substance P-containing neurons is slightly decreased.
