NEURONAL SPROUTING IN MOUSE SENSORY GANGLIA INFECTED WITH HERPES-SIMPLEX VIRUS TYPE-2 (HSV-2) - INDUCTION OF GROWTH-ASSOCIATED PROTEIN (GAP-43) AND ULTRASTRUCTURAL EVIDENCE

Herpes simplex virus (HSV) is neurotropic and when inoculated on the m ouse footpad is retrogradely transported to the associated dorsal root ganglia (DRG), where infection is established. Previous observations suggest that, after HSV infection, sensory ganglion neurons may mount a sprouting response, In our HSV-infected DRG model, we investigate th is issue by (1) examining expression of growth-associated protein (GAP -43), a molecule known to be induced by growing axons, and (2) determi ning ultrastructurally whether HSV-infected dorsal roots contain neuri tes, In a time course study, we show that GAP-43 is induced both in HS V-infected DRG and their central processes, The increase in GAP-43 is first seen 2 weeks following unilateral footpad inoculation in both ce ll bodies and dorsal roots, and is sustained at 1 month post inoculati on in roots but not in perikarya. Large bundles of unmyelinated small caliber axons, lacking Schwann cell ensheathment, are observed by elec tron microscopy in dorsal roots 2 weeks and 1 month following inoculat ion, These profiles resemble developing or regenerating neurites and a re rarely seen in roots of mock-infected or uninfected controls. The i ncreased GAP-43 immunoreactivity and ultrastructural changes shown her e, in conjunction with previously documented selective neuropeptide an d enzyme alterations, confirm that a sprouting response is mounted in sensory ganglia following acute HSV infection.