Vimentin-positive astrocytes in canine distemper: a target for canine distemper virus especially in chronic demyelinating lesions?
Vimentin-positive astrocytes in canine distemper: a target for canine distemper virus especially in chronic demyelinating lesions?
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犬瘟热中波形蛋白阳性星形胶质细胞：犬瘟热病毒的靶标，尤其是慢性脱髓鞘病变？
DOI：
10.1007/s00401-007-0307-5
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发表时间：
2007
影响因子：
12.7
通讯作者：
W. Baumgärtner
中科院分区：
文献类型：
--
作者：
F. Seehusen;E. Orlando;K. Wewetzer;W. Baumgärtner
在由犬瘟热病毒(CDV)引起的犬瘟热脱髓鞘白质脑炎(DL)中，星形胶质细胞是主要的病毒靶标。在这些细胞中，胶质纤维酸性蛋白(GFAP)是主要的中间纤维，而Vimentin早期出现在星形细胞谱系中，并逐渐被GFAP取代。为了进一步研究多发性硬化症模型犬脑星形细胞感染的作用，对福尔马林固定石蜡包埋的小脑进行了免疫组织化学和免疫荧光研究。CDV感染犬混合脑细胞培养的免疫荧光研究也确定了这些中间丝的表达和形态变化。在急性瘟热皮损中，星形细胞反应主要由GFAP和CDV阳性细胞组成。相反，Vimentin阳性的星形细胞样细胞出现在晚期皮损中，这是携带病原体的主要细胞类型，表明CDV脑脊髓炎病变进展过程中胶质细胞的趋向性和/或易感性发生了变化。犬细胞培养物由GFAP阳性的星形胶质细胞、Vimentin阳性细胞和其他胶质细胞组成。在CDV-R252株感染后，GFAP阳性的星形胶质细胞，特别是多核合体巨细胞，显示出细胞骨架的破坏，而Vimentin阳性的细胞，尽管感染更频繁，但丝网没有任何变化。这表明，与未成熟的波形蛋白阳性的星形胶质细胞相比，成熟的GFAP阳性星形胶质细胞的易感性更高。然而，后者表现出对CDV的易感性增加。综上所述，本研究结果提示CDV细胞嗜性的改变和/或分化较低的星形胶质细胞的出现代表了病毒感染的永久来源和在晚期DL皮损中的扩散。
In canine distemper demyelinating leukoencephalitis (DL), caused by canine distemper virus (CDV), astrocytes represent the main virus target. In these cells, glial fibrillary acidic protein (GFAP) is the main intermediate filament, whereas vimentin occurs early in the astrocytic lineage and is replaced gradually by GFAP. To further characterize the role of astrocytic infection in dogs with DL, an animal model for multiple sclerosis, formalin-fixed paraffin-embedded cerebella were investigated immunohistochemically and by immunofluorescence. The expression and morphological alterations of these intermediate filaments were also determined by immunofluorescence studies of CDV-infected canine mixed brain cell cultures. In acute distemper lesions, the astrocytic response was mainly composed of GFAP- and CDV-positive cells. In contrast, vimentin-positive astrocyte-like cells were present in advanced lesions, which represented the main cell type harboring the pathogen, indicating a change in cell tropism and/or susceptibility of glial cells during lesion progression in CDV encephalomyelitis. Canine cell cultures were composed of GFAP-positive astrocytes, vimentin-positive cells and other glial cells. Following infection with the CDV-R252 strain, GFAP-positive astrocytes, especially multinucleated syncytial giant cells, displayed a disrupted cytoskeleton, whereas vimentin-positive cells though more frequently infected did not show any alteration in the filament network. This indicates increased vulnerability of mature GFAP-positive astrocytes compared to immature, vimentin-positive astrocytes. The latter, however, exhibited increased susceptibility to CDV. To conclude, the present findings indicate a change in cell tropism of CDV and/or the occurrence of less differentiated astrocytes representing a permanent source for virus infection and spread in advanced lesions of DL.