Altered expression and changing distribution of the nerve growth associated protein GAP-43 during ocular HSV-1...

This research examines changes that occur in neurons during corneal herpes simplex virus (HSV-1) infection and focuses on the nerve growth associated protein GAP-43. Cornea and trigeminal ganglion (TG) of New Zealand white rabbits were examined after inoculation of the McKrae and 17 Syn+ strains of HSV-1 to the cornea. Rabbit tissues were taken during acute, latent and induced reactivation stages of infection. Systemic immunosuppression (intravenous injections of cyclophosphamide and dexamethasone) was used to induce reactivation. Western blotting, immunoblotting and autoradiography with the same antibody were used respectively to verify antibody specificity, measure changes in GAP-43 concentration and localize GAP-43 to neurons in the TG. During acute infection, corneal GAP-43 increased significantly while no change was seen in the TG. GAP-43 content was elevated in TG and cornea during viral latency (post-inoculation days 84-154) for both HSV-1 strains. When latent virus was reactivated, the corneal concentration of GAP-43 was more than double that of normal rabbits and the concentration of GAP-43 in TG was reduced compared to the non-reactivated, latently-infected TG. In summary, HSV-1 infected TG neurons expressed more GAP-43 than control neurons and immunosuppressive therapy led not only to viral reactivation and increased GAP-43 concentrations in cornea but also to decreased GAP-43 concentrations in TG. These results suggest that factors which maintain HSV-1 latency and induce reactivation could be linked to elements regulating GAP-43 expression.