Czub S, Lynch W P, Czub M, Portis J L
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana.
Lab Invest. 1994 May;70(5):711-23.
A chimeric murine retrovirus, FrCasE, causes a rapid noninflammatory spongiform neurodegenerative disease of the motor system with an incubation period of 15 to 16 days after neonatal inoculation. Neurovirulence is determined by the viral envelope gene, but the neurodegeneration is an indirect consequence of virus infection, because the neurons that degenerate appear not to be infected.
The current study was undertaken to compare the kinetics of lesion development and the expression of viral envelope protein in the central nervous system (CNS). Neonatal mice were inoculated with FrCasE intraperitoneally and were killed at various times for determination of the kinetics of the CNS infection, the distribution of lesion in the CNS, and the distribution of viral envelope protein. In addition, qualitative features of both viral envelope and gag proteins were followed by immunoblot analysis.
The lesions induced by FrCasE consisted of vacuolar degeneration but without associated astrocytosis, the lack of an astroglial response being a consequence of the rapidity of the disease process. Vacuoles were observed primarily in the neuropil of the motor centers of spinal cord, brain stem, and cerebral cortex. Lesions appeared in all of these areas during a narrow window of time (< or = 3 days). Cells in which viral envelope protein was detected by immunohistochemistry before the appearance of spongiform degeneration included premigratory cerebellar cortical granule neurons as well as vascular elements in the regions that would ultimately exhibit spongiform degeneration. Two forms of viral envelope protein were detected in the CNS. A 70-kilodalton species appeared first, followed by an approximately 64-kilodalton species, which was detected coincident with the first appearance of spongiform lesions.
Astrocytosis is a secondary reaction to the neuronal cytopathology induced by FrCasE and appears to be dependent on the developmental state of the CNS. The abrupt, diffuse nature of lesion development in this disease suggests a global effect of the virus infection. Cells of the CNS vasculature (either endothelial cells, perivascular microglial cells, or both) as well as cerebellar granule neurons appear to be seminally involved in the pathogenesis of the spongiform degeneration. The two species of viral envelope protein appear to be expressed by different cell types in the CNS.
一种嵌合型鼠逆转录病毒FrCasE可引发运动系统快速的非炎性海绵状神经退行性疾病，新生小鼠接种后潜伏期为15至16天。神经毒力由病毒包膜基因决定，但神经退行性变是病毒感染的间接后果，因为发生退变的神经元似乎未被感染。
本研究旨在比较病变发展动力学以及病毒包膜蛋白在中枢神经系统（CNS）中的表达。新生小鼠经腹腔接种FrCasE，并在不同时间处死，以确定CNS感染动力学、CNS中病变分布以及病毒包膜蛋白分布。此外，通过免疫印迹分析追踪病毒包膜蛋白和gag蛋白的定性特征。
FrCasE诱导的病变包括空泡变性，但无相关星形细胞增生，缺乏星形胶质细胞反应是疾病进程快速的结果。空泡主要在脊髓、脑干和大脑皮质运动中枢的神经毡中观察到。在狭窄的时间段内（≤3天），所有这些区域均出现病变。在海绵状变性出现之前，通过免疫组织化学检测到病毒包膜蛋白的细胞包括迁移前的小脑皮质颗粒神经元以及最终会出现海绵状变性区域的血管成分。在CNS中检测到两种形式的病毒包膜蛋白。首先出现一种70千道尔顿的蛋白，随后出现一种约64千道尔顿的蛋白，其与海绵状病变的首次出现同时被检测到。
星形细胞增生是对FrCasE诱导的神经元细胞病理学的继发反应，似乎取决于CNS的发育状态。该疾病中病变发展的突然、弥漫性质表明病毒感染具有整体效应。CNS脉管系统的细胞（内皮细胞、血管周围小胶质细胞或两者）以及小脑颗粒神经元似乎在海绵状变性的发病机制中起关键作用。两种病毒包膜蛋白似乎由CNS中的不同细胞类型表达。
