Pennington Matthew R, Fort Michael W, Ledbetter Eric C, Van de Walle Gerlinde R
Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca NY 14853, United States.
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca NY 14853, United States.
J Gen Virol. 2016 Jun;97(6):1414-1425. doi: 10.1099/jgv.0.000451. Epub 2016 Mar 9.
Feline herpesvirus type-1 (FHV-1) is the most common viral cause of ocular surface disease in cats. Many antiviral drugs are used to treat FHV-1, but require frequent topical application and most lack well-controlled in vivo studies to justify their clinical use. Therefore, better validation of current and novel treatment options are urgently needed. Here, we report on the development of a feline whole corneal explant model that supports FHV-1 replication and thus can be used as a novel model system to evaluate the efficacy of antiviral drugs. The anti-herpes nucleoside analogues cidofovir and acyclovir, which are used clinically to treat ocular herpesvirus infection in cats and have previously been evaluated in traditional two-dimensional feline cell cultures in vitro, were evaluated in this explant model. Both drugs suppressed FHV-1 replication when given every 12 h, with cidofovir showing greater efficacy. In addition, the potential efficacy of the retroviral integrase inhibitor raltegravir against FHV-1 was evaluated in cell culture as well as in the explant model. Raltegravir was not toxic to feline cells or corneas, and most significantly, inhibited FHV-1 replication at 500 µM in both systems. Importantly, this drug was effective when given only once every 24 h. Taken together, our data indicate that the feline whole corneal explant model is a useful tool for the evaluation of antiviral drugs and, furthermore, that raltegravir appears a promising novel antiviral drug to treat ocular herpesvirus infection in cats.
猫疱疹病毒1型（FHV-1）是猫眼部表面疾病最常见的病毒病因。许多抗病毒药物被用于治疗FHV-1，但需要频繁局部应用，且大多数缺乏充分对照的体内研究来证明其临床应用的合理性。因此，迫切需要更好地验证当前和新型治疗方案。在此，我们报告了一种猫全角膜外植体模型的开发，该模型支持FHV-1复制，因此可作为一种新型模型系统来评估抗病毒药物的疗效。临床上用于治疗猫眼部疱疹病毒感染且此前已在传统二维猫细胞培养物中进行体外评估的抗疱疹核苷类似物西多福韦和阿昔洛韦，在该外植体模型中进行了评估。两种药物每12小时给药一次时均能抑制FHV-1复制，西多福韦显示出更高的疗效。此外，还在细胞培养物以及外植体模型中评估了逆转录病毒整合酶抑制剂拉替拉韦对FHV-1的潜在疗效。拉替拉韦对猫细胞或角膜无毒，最重要的是，在两个系统中500µM时均能抑制FHV-1复制。重要的是，该药物每24小时仅给药一次时就有效。综上所述，我们的数据表明猫全角膜外植体模型是评估抗病毒药物的有用工具，此外，拉替拉韦似乎是一种有前景的新型抗病毒药物，可用于治疗猫眼部疱疹病毒感染。
