Gravel C, Kay D G, Jolicoeur P
Laboratory of Molecular Biology, Institut de Recherches Cliniques de Montréal, Quebec, Canada.
J Virol. 1993 Nov;67(11):6648-58. doi: 10.1128/JVI.67.11.6648-6658.1993.
The Cas-Br-E murine leukemia virus (MuLV) induces a progressive hindlimb paralysis accompanied by a spongiform myeloencephalopathy in susceptible mice. In order to better understand the pathological process leading to these neurodegenerative lesions, we have investigated the nature of the cell type(s) infected by the virus during the course of the disease in CFW/D and SWR/J mice. For this purpose, we used in situ hybridization with virus-specific probes in combination with cell-type-specific histochemical (lectin) and immunological markers as well as morphological assessment. In the early stage of infection, endothelial cells represented the main cell type expressing viral RNA in the central nervous system (CNS). With disease progression and the appearance of lesions, microglial cells became the major cell type infected, accounting for up to 65% of the total infected cell population in diseased areas. Morphologically, these cells appeared activated and were frequently found in clusters. Infection and activation of microglial cells were almost exclusively restricted to diseased regions of the CNS. Neurons in diseased regions were not discernibly infected with virus at either early or late times of disease progression. Similarly, the proportion of infected astrocytes was typically < 1%. Although some endothelial cells and oligodendrocytes were infected by the virus, their infection was not limited to diseased CNS regions. These results are consistent with a model of indirect motor neuron degeneration, subsequent to the infection of nonneuronal CNS cells and especially of microglial cells. Infected microglial cells may play a role in the disease process by releasing not only virions or viral env-gene-encoded gp70 proteins but also other factors which may be directly or indirectly toxic to neurons. Parallels between microglial cell infection by MuLV and by lentiviruses, and specifically by human immunodeficiency virus, are discussed.
卡斯-布-埃氏鼠白血病病毒（MuLV）可诱导易感小鼠出现进行性后肢麻痹，并伴有海绵状脑脊髓病。为了更好地理解导致这些神经退行性病变的病理过程，我们研究了CFW/D和SWR/J小鼠在疾病过程中被该病毒感染的细胞类型的性质。为此，我们将病毒特异性探针原位杂交与细胞类型特异性组织化学（凝集素）和免疫标记以及形态学评估相结合。在感染早期，内皮细胞是中枢神经系统（CNS）中表达病毒RNA的主要细胞类型。随着疾病进展和病变出现，小胶质细胞成为主要被感染的细胞类型，在病变区域占总感染细胞群体的比例高达65%。从形态学上看，这些细胞呈现活化状态，且经常成簇出现。小胶质细胞的感染和活化几乎完全局限于CNS的病变区域。在疾病进展的早期或晚期，病变区域的神经元均未明显感染病毒。同样，被感染的星形胶质细胞比例通常<1%。虽然一些内皮细胞和少突胶质细胞被该病毒感染，但其感染并不局限于CNS的病变区域。这些结果与非神经元CNS细胞尤其是小胶质细胞感染后间接运动神经元变性的模型一致。被感染的小胶质细胞可能通过不仅释放病毒粒子或病毒env基因编码的gp70蛋白，还释放其他可能对神经元直接或间接有毒的因子，在疾病过程中发挥作用。文中还讨论了MuLV与慢病毒，特别是与人类免疫缺陷病毒感染小胶质细胞之间的相似之处。
