Conjunctivitis in rabbits caused by enterovirus type 70 (EV70)

A rabbit enterovirus 70 (EV70) model infection that closely mimics human enteroviral conjunctivitis was developed. Conjunctivitis occurred 24 hr following topical application of EV70. The conjunctivitis was characterized by tearing, redness, swelling of the eye lids, follicles in the superior palpebral conjunctiva, and dilatation of subconjunctival blood vessels. Histologic examination of conjunctival and corneal tissue taken 1 and 2 days after infection revealed numerous punctate areas devoid of squamous epithelium on the upper palpebral conjunctiva. Also, follicles without germinal centers were observed microscopically in the palpebral and tarsal conjunctiva. Fibroblast infiltration characteristic of wound healing and a sparse mononuclear infiltration was noted by the second day. Peak levels of virus [10(3) to 10(6.2) plaque forming units (PFU)/ml] were detected 1 to 2 days after infection and declined to undetectable levels after 3 to 5 days. Interestingly, antiserum to parental EV70 was less effective (8-10-fold) in neutralizing EV70 adapted to animal and tissue culture systems. This finding suggests that an antigenic variant of EV70 arose during adaptation. Fibroblast interferon (IFN beta), which is indicative of viral infection, was detected in tears from 6 of 16 rabbits and declined to undetectable levels 3 days after infection. Serum antibody to EV70 was detectable 8 to 10 days after infection. However, the level of serum antibody was highly variable. The results indicate that the clinical disease, virologic and immunologic courses were similar to that of the human infection. Results suggest that this animal model provides a system for studying the natural antigenic variation of EV70, the natural host defenses of the eye, and antiviral treatments against enteroviral conjunctivitis.