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

被引:5
作者
Lewin, Andrew C. [1 ]
Ineck, Nikole E. [1 ]
Mironovich, Melanie A. [1 ]
Marino, Morgan E. [1 ]
Liu, Chin-Chi [1 ]
Emelogu, Ugochi [1 ]
Mills, Erinn P. [1 ]
Camacho-Luna, Pilar [1 ]
Carter, Renee T. [1 ]
机构
[1] Louisiana State Univ, Sch Vet Med, Dept Vet Clin Sci, Baton Rouge, LA 70803 USA
关键词
feline herpesvirus; cidofovir; famciclovir; ganciclovir; antiviral; resistance; mutation; genomics; SIMPLEX-VIRUS RESISTANCE; ACYCLOVIR; PENCICLOVIR; FAMCICLOVIR; SEQUENCE; GANCICLOVIR; CIDOFOVIR; VARIANTS; HSV-1; DRUGS;
D O I
10.3389/fvets.2023.1197249
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
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 (n = 3), cidofovir 0.5% ophthalmic solution (n = 3), famciclovir oral solution (n = 5), or ganciclovir 0.15% ophthalmic solution (n = 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 (p = 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 IC50 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.
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页数:8
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