The antiviral resistance and replication of cidofovir-resistant adenovirusvariants in the New Zealand White rabbit ocular model

PURPOSE. TO determine the antiviral resistance of three cidofovir (CDV)-res istant variants of adenovirus type 5 (Ad5) and their ability to replicate i n the New Zealand White rabbit ocular model. METHODS. Rabbits were inoculated topically in both eyes with the CDV-resist ant variants R1, R2, and R3, and the Ad5 parental strain. On day 1, rabbits from each virus inoculation were divided into two topical treatment groups : 0.5% CDV and PBS control. Treatment was administered twice daily in both eyes for 7 days. Ah eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Using viral outcome parameters, CDV resistance was determine d for each virus by comparing each CDV-treated virus group to its respectiv e PBS control, and altered pathogenesis was assessed by comparing viral rep lication in the PBS control groups of the Ad5 parent and the three resistan t variants. RESULTS. Topical 0.5% CDV treatment demonstrated significant antiviral inhi bitory activity in the Ad5 parental group (e.g., reduced total Ad5-positive cultures, reduced daily Ad5-positive cultures on days 5, 9, 11, and 14, an d duration of ocular shedding), but had no effect on the three CDV-resistan t variants. There were no significant differences in pathogenicity between the Ad5 parent and the CDV-resistant variants. CONCLUSIONS. The Ad5 variants R1, R2, and R3 were resistant to topical trea tment with 0.5% cidofovir in the rabbit ocular model. However, the acquisit ion of CDV resistance did not alter the replication of the three Ad5 CDV va riants on the rabbit eye.