Abstract

Infections with feline herpesvirus type 1 (FeHV-1) are frequently associated with recurrent ocular disease, which may occur even in vaccinated cats. The underlying
pathogenesis is poorly understood. Specifically, the role of circulating, superinfecting virus strains is unknown. To begin addressing this complex question, we reconstituted a
marker-taggedmutant FeHV-1 from a bacterial artificial chromosome (BAC) harboring the FeHV-1 genome. This mutant was deleted for the glycoprotein G gene (DgG) but carried
instead a gene encoding the green fluorescent protein (GFP). Nine latently with wild-type (wt) FeHV-1-infected cats were superinfected with this mutant and monitored for clinical, virological, and immunological parameters.
While the mutant virus replicated locally, induced a rise in neutralizing antibody titers, and stimulated the interferon system, no evidence for ocular illness or reactivation of the underlying wtFeHV-1-infection was detected. However, cyclophosphamide–dexamethasone (C–D) treatment, applied 16 months after the superinfection, was able to reactivate wtFeHV-1. Reactivation was accompanied by recrudescence of ocular disease signs. In contrast, reactivation of the superinfecting mutant virus was not detected. Since kittens are normally infected with wtFeHV-1 prior to the first immunization, the data described in this study may be valuable for designing future live attenuated FeHV-1 vaccines.