Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
Virus Res. 2010 Feb;147(2):176-81. doi: 10.1016/j.virusres.2009.10.017. Epub 2009 Nov 5.
Available vaccines fail to induce lasting and protective immunity to equine herpesvirus 1 (EHV-1) associated diseases. RNA interference is a novel approach showing promise for therapeutic use in outbreak situations. This study examined the effect of small interfering RNA (siRNA) on clinical signs as well as the presence of live virus and viral DNA in nasal secretions and peripheral blood mononuclear cells (PBMCs) in horses experimentally infected with EHV-1. siRNA targeting two EHV-1 genes (glycoprotein B and the origin binding protein) was administered 12h before and 12h after intranasal infection with EHV-1. Control horses received siRNA targeting firefly luciferase. A significantly smaller proportion (0/10) of horses receiving siRNA targeting viral genes required euthanasia due to intractable neurologic disease as compared to horses in the control group (3/4; p=0.01). There was no significant difference in the presence of live virus or viral DNA in the nasal secretions or PBMCs between the two groups. Future studies are necessary to define the relative contributions of host and virus factors in the development of the neurological form of the infection and to determine an optimal dosing regimen for metaphylactic or therapeutic use of siRNA for treating EHV-1 infection.
现有的疫苗未能诱导针对马疱疹病毒 1（EHV-1）相关疾病的持久和保护性免疫。RNA 干扰是一种有前途的治疗方法，可用于爆发情况。本研究检查了小干扰 RNA（siRNA）对临床症状以及鼻腔分泌物和外周血单核细胞（PBMC）中活病毒和病毒 DNA 存在的影响，这些马匹在实验中感染了 EHV-1。在 EHV-1 鼻腔感染前 12 小时和感染后 12 小时，用针对两种 EHV-1 基因（糖蛋白 B 和起始结合蛋白）的 siRNA 进行治疗。对照组马匹接受针对萤火虫荧光素酶的 siRNA。与对照组（3/4；p=0.01）相比，接受针对病毒基因的 siRNA 治疗的马匹因难以治疗的神经系统疾病而需要安乐死的比例明显较小（0/10）。两组之间在鼻腔分泌物或 PBMC 中活病毒或病毒 DNA 的存在没有显著差异。未来的研究需要确定宿主和病毒因素在感染的神经形式发展中的相对贡献，并确定用于治疗 EHV-1 感染的 siRNA 的预防或治疗性使用的最佳剂量方案。
