Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
Vet Res. 2013 Dec 5;44(1):118. doi: 10.1186/1297-9716-44-118.
Equine herpesvirus myeloencephalitis (EHM) remains one of the most devastating manifestations of equine herpesvirus type 1 (EHV-1) infection but our understanding of its pathogenesis remains rudimentary, partly because of a lack of adequate experimental models. EHV-1 infection of the ocular vasculature may offer an alternative model as EHV-1-induced chorioretinopathy appears to occur in a significant number of horses, and the pathogenesis of EHM and ocular EHV-1 may be similar. To investigate the potential of ocular EHV-1 as a model for EHM, and to determine the frequency of ocular EHV-1, our goal was to study: (1) Dissemination of virus following acute infection, (2) Development and frequency of ocular lesions following infection, and (3) Utility of a GFP-expressing virus for localization of the virus in vivo. Viral antigen could be detected following acute infection in ocular tissues and the central nervous system (experiment 1). Furthermore, EHV-1 infection resulted in multifocal choroidal lesions in 90% (experiment 2) and 50% (experiment 3) of experimentally infected horses, however ocular lesions did not appear in vivo until between 3 weeks and 3 months post-infection. Taken together, the timing of the appearance of lesions and their ophthalmoscopic features suggest that their pathogenesis may involve ischemic injury to the chorioretina following viremic delivery of virus to the eye, mirroring the vascular events that result in EHM. In summary, we show that the frequency of ocular EHV-1 is 50-90% following experimental infection making this model attractive for testing future vaccines or therapeutics in an immunologically relevant age group.
马疱疹病毒脑脊髓炎(EHM)仍然是 1 型马疱疹病毒(EHV-1)感染最具破坏性的表现之一,但我们对其发病机制的理解仍然很基础,部分原因是缺乏足够的实验模型。EHV-1 对眼部血管的感染可能提供了另一种模型,因为 EHV-1 引起的脉络膜视网膜炎似乎在大量马中发生,并且 EHM 和眼部 EHV-1 的发病机制可能相似。为了研究眼部 EHV-1 作为 EHM 模型的潜力,并确定眼部 EHV-1 的频率,我们的目标是研究:(1)急性感染后病毒的传播,(2)感染后眼部病变的发展和频率,以及(3)GFP 表达病毒用于体内病毒定位的实用性。在眼部组织和中枢神经系统中可以检测到急性感染后的病毒抗原(实验 1)。此外,EHV-1 感染导致 90%(实验 2)和 50%(实验 3)的实验感染马出现多灶性脉络膜病变,然而,眼部病变直到感染后 3 周到 3 个月才在体内出现。总之,病变出现的时间及其眼科特征表明,它们的发病机制可能涉及病毒血症向眼部输送病毒后对脉络膜视网膜的缺血性损伤,反映了导致 EHM 的血管事件。综上所述,我们表明,实验感染后眼部 EHV-1 的频率为 50-90%,这使得该模型成为在免疫相关年龄段测试未来疫苗或治疗药物的有吸引力的选择。