This project investigates neural regenerative responses to herpesvirus infection. Initial studies examine the effects of herpes simplex virus type-2 (HSV-2) infection on host dorsal root ganglia (DRG) in a mouse footpad inoculation model, as well as the effects of herpes simplex virus type-1 (HSV-l) infection on host trigeminal ganglia in a mouse corneal inoculation model. These experimental models of peripheral infection mimic many aspects of human clinical HSV infection. During FY 1992, the focus of this project was on biological changes that occur in host sensory ganglion neurons as the result of viral infection. Specifically, the following issues were addressed: 1) Is there neuronal death as a result of HSV infection? 2) Does HSV infection alter normal neuropeptide production in the host sensory ganglia? 3) Can neurobiological alterations, that have been shown in other regeneration models, be identified in this system? Major findings are: 1) Neuronal death occurs in sensory ganglia as a result of HSV infection. 2) There is selective modulation of host cell neuropeptides during the course of infection. Galanin, normally undetectable in adult sensory neurons, is selectively expressed following both footpad and corneal inoculation with HSV-2 and HSV-1, respectively, while the neuropeptides calcitonin gene-related peptide and neuropeptide Y do not appear to be affected. 3) Other regeneration-associated markers, such as growth-associated protein, appear altered and promise to provide insight into the effects of HSV infection on the neurobiology of host ganglionic neurons.
