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Eric G. Romanowski, Y. Jerold Gordon, Trinita Araullo-Cruz, Kathleen A. Yates, Paul R. Kinchington; The Antiviral Resistance and Replication of Cidofovir-Resistant Adenovirus Variants in the New Zealand White Rabbit Ocular Model. Invest. Ophthalmol. Vis. Sci. 2001;42(8):1812-1815.
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purpose. To determine the antiviral resistance of three cidofovir
(CDV)-resistant variants of adenovirus type 5 (Ad5) and their ability
to replicate in the New Zealand White rabbit ocular model.
methods. Rabbits were inoculated topically in both eyes with the CDV-resistant
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. All eyes were cultured for virus on days
0, 1, 3, 4, 5, 7, 9, 11, and 14. Using viral outcome parameters, CDV
resistance was determined for each virus by comparing each CDV-treated
virus group to its respective PBS control, and altered pathogenesis was
assessed by comparing viral replication in the PBS control groups of
the Ad5 parent and the three resistant variants.
results. Topical 0.5% CDV treatment demonstrated significant antiviral
inhibitory 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, and duration of ocular shedding), but had no effect on
the three CDV-resistant 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 treatment
with 0.5% cidofovir in the rabbit ocular model. However, the
acquisition of CDV resistance did not alter the replication of the
three Ad5 CDV variants on the rabbit eye.
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