Chowdhury S I, Lee B J, Ozkul A, Weiss M L
Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506, USA.
J Virol. 2000 Mar;74(5):2094-106. doi: 10.1128/jvi.74.5.2094-2106.2000.
Glycoprotein E (gE) is important for full virulence potential of the alphaherpesviruses in both natural and laboratory hosts. The gE sequence of the neurovirulent bovine herpesvirus 5 (BHV-5) was determined and compared with that of the nonneurovirulent BHV-1. Alignment of the predicted amino acid sequences of BHV-1 and BHV-5 gE open reading frames showed that they had 72% identity and 77% similarity. To determine the role of gE in the differential neuropathogenesis of BHV-1 and BHV-5, we have constructed BHV-1 and BHV-5 recombinants: gE-deleted BHV-5 (BHV-5gEDelta), BHV-5 expressing BHV-1 gE (BHV-5gE1), and BHV-1 expressing BHV-5 gE (BHV-1gE5). Neurovirulence properties of these recombinant viruses were analyzed using a rabbit seizure model (S. I. Chowdhury et al., J. Comp. Pathol. 117:295-310, 1997) that distinguished wild-type BHV-1 and -5 based on their differential neuropathogenesis. Intranasal inoculation of BHV-5 gEDelta and BHV-5gE1 produced significantly reduced neurological signs that affected only 10% of the infected rabbits. The recombinant BHV-1gE5 did not invade the central nervous system (CNS). Virus isolation and immunohistochemistry data suggest that these recombinants replicate and spread significantly less efficiently in the brain than BHV-5 gE revertant or wild-type BHV-5, which produced severe neurological signs in 70 to 80% rabbits. Taken together, the results of neurological signs, brain lesions, virus isolation, and immunohistochemistry indicate that BHV-5 gE is important for efficient neural spread and neurovirulence within the CNS and could not be replaced by BHV-1 gE. However, BHV-5 gE is not required for initial viral entry into olfactory pathway.
糖蛋白E（gE）对于α疱疹病毒在天然宿主和实验室宿主中的完全毒力潜能都很重要。测定了神经毒力牛疱疹病毒5（BHV-5）的gE序列，并与非神经毒力的BHV-1的gE序列进行了比较。BHV-1和BHV-5 gE开放阅读框的预测氨基酸序列比对显示，它们具有72%的同一性和77%的相似性。为了确定gE在BHV-1和BHV-5不同神经发病机制中的作用，我们构建了BHV-1和BHV-5重组体：缺失gE的BHV-5（BHV-5gEDelta）、表达BHV-1 gE的BHV-5（BHV-5gE1）以及表达BHV-5 gE的BHV-1（BHV-1gE5）。使用兔癫痫模型（S. I. Chowdhury等人，《比较病理学杂志》117:295 - 310, 1997）分析了这些重组病毒的神经毒力特性，该模型根据野生型BHV-1和 -5不同的神经发病机制对它们进行区分。经鼻接种BHV-5 gEDelta和BHV-5gE1产生的神经症状明显减轻——仅10%的感染兔受到影响。重组体BHV-1gE5未侵入中枢神经系统（CNS）。病毒分离和免疫组织化学数据表明，这些重组体在脑中的复制和传播效率明显低于BHV-5 gE回复株或野生型BHV-5，后者在70%至80%的兔中产生严重的神经症状。综合神经症状、脑损伤、病毒分离和免疫组织化学的结果表明，BHV-5 gE对于在CNS内高效的神经传播和神经毒力很重要，并且不能被BHV-1 gE替代。然而，BHV-5 gE对于病毒最初进入嗅觉通路并非必需。
