Multiple adenoviral serotypes demonstrate host range extension in the New Zealand rabbit ocular model

Although several human adenoviral serotypes demonstrated the genetic capability of replicating in New Zealand rabbit corneas in organ culture, only a single adenovirus (Ad) serotype, Ad5, has been reported to replicate in vivo in New Zealand rabbit eyes. The purpose of this study was to determine whether additional adenoviral serotypes could extend their host range to the New Zealand rabbit ocular model.

Six rabbits per viral isolate were inoculated in each eye after corneal scarification with 1.5 x 10(6) plaque-forming units per eye with one of the following reference or clinical adenovirus isolates: Ad1 ATCC, Ad1 Kmetz, Ad2 ATCC, Ad2 Wolf, Ad5 ATCC, Ad5 McEwen, Ad6 ATCC, Ad 19 ATCC, and Ad8 Cray (five rabbits). Eyes were cultured on days 0, 1, 3, 4, 5, 7, 9, 11, 14, 16, 18, and 21 after inoculation, and their tear film viral titers were determined on A549 cells.

Ad19 ATCC and Ad8 Cray demonstrated no apparent viral replication. The mean duration of shedding was 1.5 and 0.3 days, respectively, and the total percentage of Ad-positive eyes was 13% and 3%, respectively. In contrast to Ad19 ATCC and Ad8 Cray, all other isolates demonstrated productive infection. The mean duration of shedding was 8 to 16 days (P < 0.0001), and the total percentage of Ad-positive eyes was 33% to 79% (P < 0.0002). The durations of shedding for Ad1 ATCC, Ad1 Kmetz, Ad2 ATCC, Ad2 Wolf, and Ad6 ATCC did not differ statistically from Ad5 McEwen, whereas Ad5 ATCC demonstrated a duration of shedding longer than all isolates (P < 0.0001).

This was the first demonstration of host range extension by additional clinical and reference isolates of adenovirus types 1, 2, 5, and 6 in the New Zealand rabbit ocular model. These results suggested that host specificity was less stringent than previously thought.