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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.
Insights
Passive immunization improved a mouse model for recurrent herpes simplex virus type 1 (HSV-1) eye disease. Reactivation treatments, including UV irradiation, successfully induced recurrent infections, mimicking human disease patterns.
Area of Science:
- Ophthalmology
- Virology
- Immunology
Background:
- Herpes simplex virus type 1 (HSV-1) can establish latent infections, leading to recurrent ocular disease.
- Recurrent herpetic eye disease poses a significant challenge in clinical management.
- Developing reliable animal models is crucial for studying HSV-1 reactivation and testing therapeutic strategies.
Purpose of the Study:
- To refine a mouse model for recurrent herpetic eye disease using passive immunization.
- To investigate the efficacy of different reactivation stimuli in inducing recurrent HSV-1 ocular infections.
- To compare the clinical manifestations and immunological responses in reactivated HSV-1 infections.
Main Methods:
- Mice were passively immunized with anti-HSV-1 serum before corneal inoculation with HSV-1.
- Latent virus was reactivated using cyclophosphamide, dexamethasone, and UV irradiation, or UV irradiation alone.
- Recurrent infection signs, including viral shedding and corneal/lid disease, were monitored.
- Corneal lesions were analyzed, and viral antigens were localized.
- Serum neutralizing antibody levels were measured.
Main Results:
- Passive immunization increased the number of mice suitable for recurrent infection induction.
- Both UV irradiation alone and combined immunosuppressive drugs with UV irradiation induced recurrent herpetic eye disease.
- Dendritic or geographic corneal ulcerations, resembling human lesions, were observed.
- Recurrent disease patterns correlated with viral antigen distribution.
- Induction of recurrent infection showed poor correlation with rising neutralizing antibody titers.
- Mice treated with immunosuppressive drugs and UV irradiation exhibited more severe, persistent ocular pathology compared to UV-only treatment.
Conclusions:
- Passive immunization significantly enhances the mouse model for recurrent herpetic eye disease.
- UV irradiation is an effective stimulus for reactivating latent HSV-1 in the cornea.
- The model effectively replicates key features of human recurrent herpetic eye disease, including lesion morphology and poor correlation with antibody response.
- The severity of recurrent disease is influenced by the reactivation stimulus, with combined immunosuppression leading to worse outcomes.
