Lesion profiling and subcellular prion localization of cervid chronic wasting disease in domestic cats.

Lesion profiling and subcellular prion localization of cervid chronic wasting disease in domestic cats.
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DOI:
10.1177/0300985814524798
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发表时间:
2015-01
影响因子:
2.4
通讯作者:
Hoover EA
Hoover EA
中科院分区:
农林科学2区
文献类型:
--
作者:
Seelig DM;Nalls AV;Flasik M;Frank V;Eaton S;Mathiason CK;Hoover EA

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慢性消耗性疾病(CWD)是一种在鹿科动物中有效传播的、致死的、进行性朊病毒病,其宿主范围尚未完全明确。虽然最近已证明远交家猫(Felis卡图斯)易受实验性CWD感染,但缺乏感染的神经病理学特征。这些信息对于在自然种间传播的情况下提供诊断能力以及深入了解种间朊病毒感染中的宿主和菌株相互作用至关重要。使用光学显微镜和免疫组织化学,我们详细描述了神经海绵体增生的地形图(“病变轮廓”)以及错误折叠的朊病毒蛋白在猫CWD(FelCWD)的初级和次级传代中的分布。我们还评估了错误折叠朊蛋白(PrPD)和中枢神经系统神经元和神经胶质细胞群之间的细胞和亚细胞关联。从这些研究中,我们(1)描述了FelCWD的新的神经病理学特征,这与鹿CWD或猫海绵状脑病(FSE)不同,(2)提供了一系列与CWD相关的种间朊病毒适应的证据。此外,我们通过共聚焦分析证明了成功的共定位PrPD与神经元,星形胶质细胞,小胶质细胞,溶酶体,和突触素,这在一定程度上,牵连这些在FelCWD的神经病理学。总之,这项工作说明了主机和应变的发展中的一个独特的FelCWD神经病理配置文件,这样的配置文件可以用来区分FelCWD和FSE的同时作用。
Chronic wasting disease (CWD) is an efficiently transmitted, fatal, and progressive prion disease of cervids with an as yet to be fully clarified host range. While outbred domestic cats (Felis catus) have recently been shown to be susceptible to experimental CWD infection, the neuropathologic features of the infection are lacking. Such information is vital to provide diagnostic power in the event of natural interspecies transmission and insights into host and strain interactions in interspecies prion infection. Using light microscopy and immunohistochemistry, we detail the topographic pattern of neural spongiosis (the “lesion profile”) and the distribution of misfolded prion protein in the primary and secondary passage of feline CWD (FelCWD). We also evaluated cellular and subcellular associations between misfolded prion protein (PrPD) and central nervous system neurons and glial cell populations. From these studies, we (1) describe the novel neuropathologic profile of FelCWD, which is distinct from either cervid CWD or feline spongiform encephalopathy (FSE), and (2) provide evidence of serial passage-associated interspecies prion adaptation. In addition, we demonstrate through confocal analysis the successful co-localization of PrPD with neurons, astrocytes, microglia, lysosomes, and synaptophysin, which, in part, implicates each of these in the neuropathology of FelCWD. In conclusion, this work illustrates the simultaneous role of both host and strain in the development of a unique FelCWD neuropathologic profile and that such a profile can be used to discriminate between FelCWD and FSE.
DOI: 10.1371/journal.pone.0004848
发表时间: 2009
期刊: PloS one
影响因子: 3.7
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