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

Abstract

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.

Integrated analysis of microRNA and messenger RNA expression profiles reveals functional microRNA in infectious bovine rhinotracheitis virus-induced mitochondrial damage in Madin-Darby bovine kidney cells

“…Author details 1 College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, China. 2 Xinjiang key Laboratory of New Drug Study and Creation for Herbivorous Animal (XJ-KLNDSCHA), Xinjiang Agricultural University, Urumqi 830052, China.…”

“…Infectious bovine rhinotracheitis virus (IBRV) or bovine herpesvirus type-1 (BoHV-1), is a double-stranded DNA virus belonging to the family Herpesviridae, subfamily Alphaherpesvirinae [ 1 ]. IBRV infection causes various cattle diseases, such as rhinitis, encephalitis, conjunctivitis, and vulvovaginitis [ 2 , 3 ]. It can also lead to abortion and immunosuppression, leading to more serious diseases.…”

Development of Matrix-Embedded Bovine Tracheal Organoids to Study the Innate Immune Response against Bovine Respiratory Disease

“…Recently, there has been advancement in using in vitro organoid culture systems as models for studying respiratory viral infections such as SARS-CoV-2 [20]. Among models for BHV-1 infection in bovines, there are air-liquid interface (ALI) cultures [17], bovine corneal cultures [21] and primary cultures derived from respiratory explants [22]. ALI culture appears to be one of the best models for its capabilities to recapitulate the diverse and complex composition of mucociliary differentiation while retaining the characteristics of the primary tissue [23,24].…”