In order to develop a new mammalian model of nervous system regeneration, for omparison with classical axotomy models, peripheral and central nervous system regenerative responses to herpesvirus infection are investigated in the mouse. Initial studies examine the effects of herpes simplex virus type~1 and type~2 (HSV~1, ~2) infection on host sensory ganglia following peripheral inoculation. This experimental model mimics many aspects of human clinical herpesvirus infection and may provide insights into mechanisms of post~herpetic neuralgia. During FY 1993, this project continued to define and examine biological changes that occur in host dorsal root ganglia (DRG) as the result of herpesvirus infection following footpad inoculation. The following issues were addressed: 1) Can neurochemical alterations, that have been demonstrated in classical regeneration models, be identified in this system? In a time course study of HSV~2 infection, alterations of growth associated protein (GAP~43), a marker usually identified with regeneration in neurons, was separately analyzed in DRG cell bodies and in their peripheral and central processes. 2) Can regenerating neurites be demonstrated in this model and do they contain GAP~43? Neurites have been observed incidentally in dorsal roots in another HSV model, but current studies aim to systematically examine this question at the ultrastructural level. Other questions include: 3) Is DRG neuronal death a general finding in HSV infection? and 4) Does EDTA tissue decalcification alter detection and quantitative evaluation of neural antig s? Findings are: 1) GAP~43 is increased in DRG and dorsal roots 14 days following footpad inoculation with HSV~2. These initial results are further evidence that, following acute ganglionic HSV~2 infection, selective neurochemical alterations can be found in DRG neurons, and another indication that the molecules that are selectively induced may relate to neuronal regeneration in this model. 2) A study documenting 60% neuronal death in DRG following HSV~2 infection was completed. In a more limited study, evidence of neuronal loss following HSV~1 infection was obtained. 3) Quantitative and qualitative analysis showed no reduction in sensitivity of neural antigen detection in EDTA~decalcified tissues. These results promise to provide insight into the effects of HSV infection on the neurobiology of the host ganglia and its connections.
