Activity of Ganciclovir Against Human Adenovirus Type-5 Infection in Cell Culture and Cotton Rat Eyes

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Abstract
The most common causes of acute viral infections of the eye for which there are no effective antiviral drugs are the adenoviruses. Until recently, pathogenesis studies and antiviral drug testing for adenovirus-induced ocular disease were not practical because no animal model was available. However, new animal models for human adenovirus-induced ocular and respiratory infections have now made such studies possible. We assessed the in vitro and in vivo activity of ganciclovir against a genetically defined adenovirus (Ad5 wt 300) known to cause severe ocular disease. The 50% inhibitory dose (ID50) values were determined by plaque reduction assays in human cells. The ID50 values of 47 and 604 microM were determined for ganciclovir and acyclovir, respectively, against Ad5, and 26 and 152 microM, respectively against Ad8. Cotton rats were inoculated bilaterally with 10(5) plaque-forming units per eye and treated topically with ganciclovir (3%, 1%, or 0.3%) or placebo for 21 days. All inoculated eyes were culture positive on days 1-3 with increased infectivity titers, regardless of treatment. However, the incidence, duration, and titer of virus shed in eyes treated with 3% ganciclovir was reduced, and the antiadenovirus enzyme-linked immunosorbent assay titers in serum were lower in these animals. Although these differences were not statistically significant, the observed trend suggested that the highest ganciclovir dose had a suppressive effect on some disease parameters.

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