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Article

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

1
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
2
Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Tohru Suzuki
Viruses 2021, 13(10), 2102; https://doi.org/10.3390/v13102102
Received: 30 August 2021 / Revised: 9 October 2021 / Accepted: 14 October 2021 / Published: 18 October 2021
(This article belongs to the Special Issue Enteric and Respiratory Viruses in Animals)
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 (n = 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 × 103 PFU/mL) versus untreated (8.25 ± 0.25 × 105 PFU/mL, p < 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. View Full-Text
Keywords: Bovine herpesvirus-1; keratoconjunctivitis; ex-vivo corneal culture; cidofovir; nucleotide analogue antiviral agent Bovine herpesvirus-1; keratoconjunctivitis; ex-vivo corneal culture; cidofovir; nucleotide analogue antiviral agent
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MDPI and ACS Style

Alling, C.R.; Liu, C.-C.; Langohr, I.M.; Haque, M.; Carter, R.T.; Baker, R.E.; Lewin, A.C. Assessment of Cidofovir for Treatment of Ocular Bovine Herpesvirus-1 Infection in Cattle Using an Ex-Vivo Model. Viruses 2021, 13, 2102. https://doi.org/10.3390/v13102102

AMA Style

Alling CR, Liu C-C, Langohr IM, Haque M, Carter RT, Baker RE, Lewin AC. Assessment of Cidofovir for Treatment of Ocular Bovine Herpesvirus-1 Infection in Cattle Using an Ex-Vivo Model. Viruses. 2021; 13(10):2102. https://doi.org/10.3390/v13102102

Chicago/Turabian Style

Alling, Christopher R., Chin-Chi Liu, Ingeborg M. Langohr, Muzammel Haque, Renee T. Carter, Rose E. Baker, and Andrew C. Lewin. 2021. "Assessment of Cidofovir for Treatment of Ocular Bovine Herpesvirus-1 Infection in Cattle Using an Ex-Vivo Model" Viruses 13, no. 10: 2102. https://doi.org/10.3390/v13102102

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