A murine model of herpes simplex virus-induced ocular disease for antiviral drug testing

Previous studies to determine the efficacy of new antiviral compounds in treating HSV ocular infections have used rabbit models. However, rabbits are expensive to purchase and maintain, and require the use of substantial amounts of test compounds. We have used the currently licensed antiviral trifluorothymidine in a murine model of HSV-induced ocular infection to demonstrate that the less expensive murine model can be used for the in vivo evaluation of potentially useful antiviral compounds. Treatment with TFT reduced the severity of blepharitis, vascularization of the cornea, stromal keratitis, and the percentage of animals developing symptoms. TFT treatment did not reduce the peak titers of infectious virus in the eyes of the infected animals, but did enhance clearance of virus from the tissues in a dose-dependent manner. Treatment with 1.0% TFT prevented the establishment of reactivatable latent infections. However, treatment with 0.01% or 0.1% TFT did not affect latency. The ED50 values for blepharitis, vascularization, and stromal keratitis ranged between 0.007% and 0.023%. These results are very similar to results obtained in rabbits and establish baseline data for comparing rabbit and murine models. This murine model provides a potentially less expensive alternative for in vivo drug testing.