Ocular inoculation of monkeys with simian varicella virus: clinical and histopathologic observations

To explore the possibility that inoculation of the eyes of African green monkeys with simian varicella virus (SVV) induces the symptoms of herpes zoster ophthalmicus (HZO), as seen in humans, and to develop a realistic and reproducible animal model of herpes zoster ophthalmicus for experimental studies.

In the first experiment, the right eyes of three African green monkeys were inoculated by intrastromal and subconjunctival injections with a suspension of SVV-infected Vero cells. In the second experiment, three additional monkeys were pretreated with intramuscular injections of methylprednisolone (41 mg/kg) for 7 days before ocular inoculation with SVV and for 3 weeks at 14 mg/kg after virus inoculation. The eyes were examined by slit-lamp biomicroscopy. Histologic, immunohistochemical, and electron microscopic studies were performed.

In the first experiment, all three animals developed high titers of anti-SVV antibodies (IgG). Diffuse stromal opacity, with keratitic precipitates, stromal edema, and mild vascularization of the cornea, appeared 12 to 14 days after inoculation. The onset of ocular disease was correlated with the rise in serum antibody levels. There was no clinical evidence of a systemic viral infection resulting from the corneal inoculations in these monkeys. In the second experiment, all three animals treated with methylprednisolone developed severe ocular pathology within 1 week of inoculation. The clinical appearance of the diseased eyes strongly indicated that local viral infection had occurred. Dendritiform keratitis, corneal erosion, and stromal necrosis with vascularization of the cornea was seen in all the eyes. The disease resolved within 4 to 5 weeks of inoculation, leaving opaque, vascularized corneas. Histologic studies showed that inflammatory cells and viral antigens were widespread throughout the diseased corneas. A high titer of anti-SVV antibody (IgG) was detected in the immunosuppressed monkeys, but no evidence of systemic viral infection was observed.

The authors propose that inoculation of the eyes of methylprednisolone-treated African green monkeys with simian varicella virus provides an appropriate animal model for studies of the virology and immunopathology of ocular varicella virus infection.