Surveillance for feline herpesvirus type 1 mutation and development of resistance in cats treated with antiviral medications

• Published in: Frontiers in veterinary science 2023-05, Vol.10, p.1197249-1197249
• Main Authors: Lewin, Andrew C, Ineck, Nikole E, Mironovich, Melanie A, Marino, Morgan E, Liu, Chin-Chi, Emelogu, Ugochi, Mills, Erinn P, Camacho-Luna, Pilar, Carter, Renee T
• Format: Article
• Language: English
• Subjects: antiviral; cidofovir; famciclovir; feline herpesvirus; ganciclovir; resistance; Veterinary Science
• ISSN: 2297-1769; 2297-1769
• DOI: 10.3389/fvets.2023.1197249

Feline herpesvirus type 1 (FHV-1) commonly causes ocular surface disease in cats and is treated with antiviral medications targeting viral DNA polymerase (UL30/42). Herein, we describe a method to assess the FHV-1 genome for mutation development and to assess the functional impact of mutations, if present. Fourteen shelter-housed domestic cats with FHV-1 ocular surface disease were assigned to one of four treatment groups: placebo (  = 3), cidofovir 0.5% ophthalmic solution (  = 3), famciclovir oral solution (  = 5), or ganciclovir 0.15% ophthalmic solution (  = 3). Swabs were collected before (day 1) and after (day 8) 1 week of twice-daily treatments to isolate viable FHV-1. Viral DNA was extracted for sequencing using Illumina MiSeq with subsequent genomic variant detection between paired day 1 and day 8 isolates. Plaque reduction assay was performed on paired isolates demonstrating non-synonymous variants. A total of 171 synonymous and 3 non-synonymous variants were identified in day 8 isolates. No variants were detected in viral UL23, UL30, or UL42 genes. Variant totals were not statistically different in animals receiving antiviral or placebo (  = 0.4997). A day 8 isolate from each antiviral treatment group contained a single non-synonymous variant in ICP4 (transcriptional regulator). These 3 isolates demonstrated no evidence of functional antiviral resistance when IC was assessed. Most (10/14 pairs) day 1 and 8 viral isolate pairs from the same host animal were near-identical. While functional variants were not detected in this small sample, these techniques can be replicated to assess FHV-1 isolates suspected of having developed resistance to antiviral medications.