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麋鹿趾间腺中的慢性消耗性疾病朊病毒。

Chronic wasting disease prions in mule deer interdigital glands.

机构信息

Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.

Centre for Prions and Protein Folding Diseases, Edmonton, Alberta, Canada.

出版信息

PLoS One. 2022 Oct 3;17(10):e0275375. doi: 10.1371/journal.pone.0275375. eCollection 2022.

Abstract

Chronic wasting disease (CWD) is a geographically expanding, fatal neurodegenerative disease in cervids. The disease can be transmitted directly (animal-animal) or indirectly via infectious prions shed into the environment. The precise mechanisms of indirect CWD transmission are unclear but known sources of the infectious prions that contaminate the environment include saliva, urine and feces. We have previously identified PrPC expression in deer interdigital glands, sac-like exocrine structures located between the digits of the hooves. In this study, we assayed for CWD prions within the interdigital glands of CWD infected deer to determine if they could serve as a source of prion shedding and potentially contribute to CWD transmission. Immunohistochemical analysis of interdigital glands from a CWD-infected female mule deer identified disease-associated PrPCWD within clusters of infiltrating leukocytes adjacent to sudoriferous and sebaceous glands, and within the acrosyringeal epidermis of a sudoriferous gland tubule. Proteinase K-resistant PrPCWD material was amplified by serial protein misfolding cyclic amplification (sPMCA) from soil retrieved from between the hoof digits of a clinically affected mule deer. Blinded testing of interdigital glands from 11 mule deer by real-time quake-induced conversion (RT-QuIC) accurately identified CWD-infected animals. The data described suggests that interdigital glands may play a role in the dissemination of CWD prions into the environment, warranting future investigation.

摘要

慢性消耗病(CWD)是一种在鹿科动物中具有地理扩张性的致命神经退行性疾病。该疾病可以直接(动物与动物之间)传播,也可以通过传染性朊病毒间接传播到环境中。间接传播 CWD 的确切机制尚不清楚,但已知污染环境的传染性朊病毒的来源包括唾液、尿液和粪便。我们之前已经在鹿的趾间腺中鉴定出 PrPC 的表达,趾间腺是位于蹄子趾间的囊状外分泌结构。在这项研究中,我们检测了感染 CWD 的鹿的趾间腺中的 CWD 朊病毒,以确定它们是否可以作为朊病毒脱落的来源,并可能有助于 CWD 的传播。对来自感染 CWD 的雌性骡鹿的趾间腺进行免疫组织化学分析,在靠近汗腺和皮脂腺的浸润性白细胞簇中以及汗腺管的表皮中鉴定出与疾病相关的 PrPCWD。通过从临床受影响的骡鹿的蹄子趾间取回的土壤中进行连续蛋白错误折叠循环扩增(sPMCA),可以扩增出对蛋白酶 K 具有抗性的 PrPCWD 物质。对来自 11 只骡鹿的趾间腺进行实时震颤诱导转化(RT-QuIC)的盲测准确地识别出了感染 CWD 的动物。描述的数据表明,趾间腺可能在 CWD 朊病毒向环境中的传播中发挥作用,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4deb/9529147/4ffd68cd42d7/pone.0275375.g001.jpg

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