title: A novel corneal explant model system to evaluate antiviral drugs against feline herpesvirus type 1 (FHV-1).
abstract: Feline herpesvirus type-1 (FHV-1) is the most common viral cause of ocular surface disease in cats. Many antiviral drugs are used to treat FHV-1, but require frequent topical application and most lack well-controlled in vivo studies to justify their clinical use. Therefore, better validation of current and novel treatment options are urgently needed. Here, we report on the development of a feline whole corneal explant model that supports FHV-1 replication and thus can be used as a novel model system to evaluate the efficacy of antiviral drugs. The anti-herpes nucleoside analogues cidofovir and acyclovir, which are used clinically to treat ocular herpesvirus infection in cats and have previously been evaluated in traditional two-dimensional feline cell cultures in vitro, were evaluated in this explant model. Both drugs suppressed FHV-1 replication when given every 12 h, with cidofovir showing greater efficacy. In addition, the potential efficacy of the retroviral integrase inhibitor raltegravir against FHV-1 was evaluated in cell culture as well as in the explant model. Raltegravir was not toxic to feline cells or corneas, and most significantly, inhibited FHV-1 replication at 500 µM in both systems. Importantly, this drug was effective when given only once every 24 h. Taken together, our data indicate that the feline whole corneal explant model is a useful tool for the evaluation of antiviral drugs and, furthermore, that raltegravir appears a promising novel antiviral drug to treat ocular herpesvirus infection in cats.
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca NY 14853, United States.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Pennington
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca NY 14853, United States.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Fort
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca NY 14853, United States.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Ledbetter
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca NY 14853, United States.
authors.forename: Gerlinde R
authors.initials: GR
authors.lastname: Van de Walle
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002415:Cats; D000077404:Cidofovir; D003315:Cornea / Q000821:virology*; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D009924:Organ Culture Techniques / Q000379:methods*; D063065:Organophosphonates / Q000494:pharmacology; D018140:Varicellovirus / Q000187:drug effects*; D014776:Virus Cultivation / Q000379:methods*
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir; D000212:Acyclovir