An improved model of recurrent herpetic eye disease in mice

Abstract

Mice were passively immunized with serum containing antibodies to herpes simplex virus type 1 (HSV-1) before inoculation on the cornea with HSV-1 strain McKrae. After such immunization most mice survived and most had normal eyes. When primary infection had subsided, mice with normal eyes were selected and treated with cyclophosphamide, dexamethasone and UV irradiation of the inoculated eye or UV irradiation alone, to reactivate latent virus. After either treatment mice developed signs of recurrent infection (virus in eyewashings and recurrent corneal and/or lid disease). The incidence of such signs was 17/33 (52%) in mice receiving immunosuppressive drugs and UV irradiation and 19/32 (59%) in mice given UV irradiation alone. In mice treated with either stimulus dendritic or geographic ulceration of the cornea was seen. These closely resembled the herpetic lesions seen in humans. There was good correlation between the pattern and distribution of recurrent corneal disease and the distribution of cells containing virus antigens in corneal epithelial sheets. Again, as in humans, the induction of recurrent infection was found to correlate poorly with a rise in the level of serum neutralizing antibody. In mice treated with UV irradiation alone corneal ulcers healed and the eyes returned to normal. By contrast, in mice given immunosuppressive drugs and UV irradiation, the ulceration became more severe and the eyes became opaque and vascularized. The use of passive immunization has greatly improved our previously reported model of recurrent herpetic eye disease since it has increased the incidence of mice suitable for the induction of recurrent infection and has increased the incidence of such infection.