Assessment of Cidofovir for Treatment of Ocular Bovine Herpesvirus-1 Infection in Cattle Using an Ex-Vivo Model

• Published in: Viruses Vol. 13; no. 10; p. 2102
• Main Authors: Alling, Christopher R, Liu, Chin-Chi, Langohr, Ingeborg M, Haque, Muzammel, Carter, Renee T, Baker, Rose E, Lewin, Andrew C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.10.2021; MDPI
• Subjects: Administration, Ophthalmic - veterinary; Animals; Antiviral Agents - pharmacology; Antiviral drugs; Bovine herpesvirus-1; Cattle; Cattle Diseases - virology; Cell culture; Cell density; Cidofovir; Cidofovir - administration & dosage; Cidofovir - pharmacology; Cornea; Cytotoxic agents; Cytotoxicity; Epithelial cells; ex-vivo corneal culture; Expenditures; Ganciclovir; Ganciclovir - administration & dosage; Ganciclovir - pharmacology; Herpesviridae Infections - drug therapy; Herpesviridae Infections - virology; Herpesvirus 1, Bovine - drug effects; Herpesvirus 1, Bovine - pathogenicity; Herpesvirus 1, Bovine - physiology; Infections; Iodine; Keratoconjunctivitis; nucleotide analogue antiviral agent; Respiratory diseases; United States > US; cidofovir; ex-vivo corneal culture; Bovine herpesvirus-1; keratoconjunctivitis; nucleotide analogue antiviral agent
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13102102

Bovine herpesvirus-1 (BoHV-1) infection contributes to keratoconjunctivitis, respiratory disease, and reproductive losses in cattle. The objective of this study was to determine the most appropriate ophthalmic antiviral agent for BoHV-1 inhibition using in-vitro culture and novel ex-vivo bovine corneal modeling. Half-maximal inhibitory concentrations of BoHV-1 were determined for cidofovir, ganciclovir, idoxuridine, and trifluridine via in-vitro plaque reduction assays. In-vitro cytotoxicity was compared amongst these compounds via luciferase assays. Trifluridine and cidofovir were the most potent BoHV-1 inhibitors in vitro, while trifluridine and idoxuridine were the most cytotoxic agents. Therefore, cidofovir was the most potent non-cytotoxic agent and was employed in the ex-vivo corneal assay. Corneoscleral rings ( = 36) from fresh cadaver bovine globes were harvested and equally divided into an uninfected, untreated control group; a BoHV-1-infected, untreated group; and a BoHV-1-infected, cidofovir-treated group. Virus isolation for BoHV-1 titers was performed from corneal tissue and liquid media. Histologic measurements of corneal thickness, epithelial cell density, and tissue organization were compared between groups. Substantial BoHV-1 replication was observed in infected, untreated corneas, but BoHV-1 titer was significantly reduced in cidofovir-treated (1.69 ± 0.08 × 10 PFU/mL) versus untreated (8.25 ± 0.25 × 10 PFU/mL, < 0.0001) tissues by day 2 of culture. No significant differences in histologic criteria were observed between groups. In conclusion, cidofovir warrants further investigation as treatment for BoHV-1 keratoconjunctivitis, with future studies needed to assess in-vivo tolerability and efficacy.