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骡鹿幼崽(白尾鹿)中慢性消耗病PrPres的口腔传播及早期淋巴嗜性

Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus).

作者信息

Sigurdson Christina J, Williams Elizabeth S, Miller Michael W, Spraker Terry R, O'Rourke Katherine I, Hoover Edward A

机构信息

Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523- 1671, USA1.

Department of Veterinary Sciences, University of Wyoming, 1174 Snowy Range Road, University of Wyoming, Laramie, WY 82070, USA 2.

出版信息

J Gen Virol. 1999 Oct;80 ( Pt 10):2757-2764. doi: 10.1099/0022-1317-80-10-2757.

DOI:10.1099/0022-1317-80-10-2757
PMID:10573172
Abstract

Mule deer fawns (Odocoileus hemionus) were inoculated orally with a brain homogenate prepared from mule deer with naturally occurring chronic wasting disease (CWD), a prion-induced transmissible spongiform encephalopathy. Fawns were necropsied and examined for PrPres, the abnormal prion protein isoform, at 10, 42, 53, 77, 78 and 80 days post-inoculation (p.i.) using an immunohistochemistry assay modified to enhance sensitivity. PrPres was detected in alimentary-tract-associated lymphoid tissues (one or more of the following: retropharyngeal lymph node, tonsil, Peyer's patch and ileocaecal lymph node) as early as 42 days p.i. and in all fawns examined thereafter (53 to 80 days p.i.). No PrPres staining was detected in lymphoid tissue of three control fawns receiving a control brain inoculum, nor was PrPres detectable in neural tissue of any fawn. PrPres-specific staining was markedly enhanced by sequential tissue treatment with formic acid, proteinase K and hydrated autoclaving prior to immunohistochemical staining with monoclonal antibody F89/160.1.5. These results indicate that CWD PrPres can be detected in lymphoid tissues draining the alimentary tract within a few weeks after oral exposure to infectious prions and may reflect the initial pathway of CWD infection in deer. The rapid infection of deer fawns following exposure by the most plausible natural route is consistent with the efficient horizontal transmission of CWD in nature and enables accelerated studies of transmission and pathogenesis in the native species.

摘要

将骡鹿幼崽(Odocoileus hemionus)经口接种由患有自然发生的慢性消耗病(CWD)的骡鹿制备的脑匀浆,CWD是一种由朊病毒引起的传染性海绵状脑病。在接种后第10、42、53、77、78和80天,使用改良以提高灵敏度的免疫组织化学分析方法对幼崽进行尸检并检测异常朊病毒蛋白异构体PrPres。最早在接种后42天在与消化道相关的淋巴组织(以下一种或多种:咽后淋巴结、扁桃体、派伊尔结和回盲淋巴结)中检测到PrPres,并且在之后检查的所有幼崽(接种后53至80天)中均检测到。在接受对照脑接种物的三只对照幼崽的淋巴组织中未检测到PrPres染色,在任何幼崽的神经组织中也未检测到PrPres。在用单克隆抗体F89/160.1.5进行免疫组织化学染色之前,通过用甲酸、蛋白酶K顺序处理组织并进行湿热高压灭菌,PrPres特异性染色明显增强。这些结果表明,在经口暴露于传染性朊病毒后的几周内,可在引流消化道的淋巴组织中检测到CWD PrPres,这可能反映了鹿中CWD感染的初始途径。通过最可能的自然途径暴露后骡鹿幼崽的快速感染与CWD在自然界中的有效水平传播一致,并能够加速对本地物种传播和发病机制的研究。

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