Holz Carine L, Nelli Rahul K, Wilson M Eilidh, Zarski Lila M, Azab Walid, Baumgardner Rachel, Osterrieder Nikolaus, Pease Anthony, Zhang Liangliang, Hession Sarah, Goehring Lutz S, Hussey Stephen B, Soboll Hussey Gisela
Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Institut für Virologie, Robert von Ostertag-Haus, Zentrum für Infektionsmedizin, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
J Gen Virol. 2017 Jun;98(6):1439-1454. doi: 10.1099/jgv.0.000773. Epub 2017 Jun 20.
Despite the importance of neurological disorders associated with herpesviruses, the mechanism by which these viruses influence the central nervous system (CNS) has not been definitively established. Owing to the limitations of studying neuropathogenicity of human herpesviruses in their natural host, many aspects of their pathogenicity and immune response are studied in animal models. Here, we present an important model system that enables studying neuropathogenicity of herpesviruses in the natural host. Equine herpesvirus type 1 (EHV-1) is an alphaherpesvirus that causes a devastating neurological disease (EHV-1 myeloencephalopathy; EHM) in horses. Like other alphaherpesviruses, our understanding of virus neuropathogenicity in the natural host beyond the essential role of viraemia is limited. In particular, information on the role of different viral proteins for virus transfer to the spinal cord endothelium in vivo is lacking. In this study, the contribution of two viral proteins, DNA polymerase (ORF30) and glycoprotein D (gD), to the pathogenicity of EHM was addressed. Furthermore, different cellular immune markers, including alpha-interferon (IFN-α), gamma-interferon (IFN-γ), interleukin-10 (IL-10) and interleukin-1 beta (IL-1β), were identified to play a role during the course of the disease.
尽管与疱疹病毒相关的神经疾病很重要，但这些病毒影响中枢神经系统（CNS）的机制尚未完全明确。由于在其自然宿主中研究人类疱疹病毒神经致病性存在局限性，其致病性和免疫反应的许多方面是在动物模型中进行研究的。在此，我们展示了一个重要的模型系统，可用于研究疱疹病毒在其自然宿主中的神经致病性。1型马疱疹病毒（EHV-1）是一种α疱疹病毒，可在马中引起毁灭性的神经疾病（EHV-1脊髓脑脊髓炎；EHM）。与其他α疱疹病毒一样，我们对病毒血症的基本作用之外的自然宿主中病毒神经致病性的了解有限。特别是，缺乏关于不同病毒蛋白在体内向脊髓内皮细胞转移病毒方面作用的信息。在本研究中，探讨了两种病毒蛋白，即DNA聚合酶（ORF30）和糖蛋白D（gD）对EHM致病性的贡献。此外，还确定了不同的细胞免疫标志物，包括α干扰素（IFN-α）、γ干扰素（IFN-γ）、白细胞介素-10（IL-10）和白细胞介素-1β（IL-1β）在疾病过程中发挥作用。
