Antiadenoviral effects of ganciclovir in types inducing keratoconjunctivitis by quantitative polymerase chain reaction methods

Abstract

Purpose: The most common external ocular viral infections are caused by several human adenovirus (HAdV) types. Ganciclovir has been reported to inhibit cytomegalovirus, herpes simplex virus types 1 and 2, varicella zoster virus, and Epstein-Barr virus. Ganciclovir ophthalmic gel, 0.15% (Virgan®) is commercially available for cytomegalovirus or herpes virus keratitis. However its inhibitory activity against HAdV is reported only for types 2 and 5. We investigated the antiadenoviral activity of ganciclovir in vitro in several common types currently inducing keratoconjunctivitis. Materials and methods: A549 cells were used for viral cell culture, and adenovirus types 3 (HAdV3; species B), 4 (species E), and 8, 19a, and 37 (species D) were used. After pretreatment of A549 with serial dilutions of ganciclovir for 24 hours, adenovirus was cultured for 7 days, and adenoviral deoxyribonucleic acid was quantitatively measured by real-time polymerase chain reaction (PCR). Results: The 50% cytotoxic concentration of ganciclovir was 212 μg/mL. The 50% effective concentration of ganciclovir obtained by real-time PCR ranged between 2.64 and 5.10 μg/mL. A significant inhibitory effect of ganciclovir on adenoviral proliferation was found in all types in a dose-dependent manner. The selectivity index of ganciclovir ranged between 41.6 and 80.3. Conclusion: Ganciclovir showed significant inhibitory activity against HAdV3, 4, 8, 19a, and 37, which induce epidemic keratoconjunctivitis. These results indicate that ganciclovir is a possible candidate for the treatment of HAdV keratoconjunctivitis, and ganciclovir ophthalmic gel could be applied to adenoviral keratoconjunctivitis in the future. © 2014 Huang et al.