VIRAL REPLICATION IS REQUIRED FOR INDUCTION OF OCULAR IMMUNOPATHOLOGYBY HERPES-SIMPLEX VIRUS

Corneal infection of BALB/c mice with herpes simplex virus type 1 resu lts in a chronic inflammatory response in the stroma termed herpetic s tromal keratitis (HSK). This disease is considered to be immunopatholo gical and mediated primarily by CD4(+) T cells of the type 1 cytokine profile, However, the nature of the antigens, virus or host derived, w hich drive the inflammatory response remains in doubt, In this study, the relevance of infection with replicating virus for the subsequent d evelopment of HSK was evaluated with immunocompetent mice as well as w ith SCID mice reconstituted with herpes simplex virus-immune CD4(+) T cells, In the corneas of immunocompetent mice, infectious virus, viral antigen, and mRNA expression were detectable for only a brief period of time (less than or equal to 7 days postinfection), and all were und etectable by the time clinical lesions were evident (10 to 15 days), V iral replication, however, was necessary for the development of HSK in both models, since infection with W-inactivated virus or with mutant viruses which were incapable of multiple rounds of replication in vivo failed to induce HSK, The inactivated and mutant viral preparations d id, however, stimulate T-cell immune responses in immunocompetent mice , The results are discussed in terms of possible involvement of host a ntigens exposed in response to transient progeny virion replication in the immune-privileged cornea.