Mother to Offspring Transmission of Chronic Wasting Disease

描述(申请人提供)：慢性消耗性疾病(CWD)是一种紧急的、有效传播的、致命的鹿(鹿、麋鹿、驼鹿)普里恩疾病，目前已在17个州、2个加拿大省份和1个亚洲国家得到确认。对鹿的流行病学研究表明，慢性萎缩性脑病是水平传播的，但令人惊讶的是，人们对其潜在的垂直传播知之甚少。是否以及如何将慢性萎缩性脑病和整个普恩病毒从母亲传给后代的问题构成了这一提议的基础。我们建议针对两个具体目标来评估垂直/母体传播是否在很大程度上解释了CWD在自然界的有效传播，方法是采用新开发的CWD感染的小型鹿颈模型，这些鹿很容易在室内设施中饲养和繁殖。我们将利用感染CWD的怀孕雌性姬鹿及其后代来确定感染CWD的普恩病毒是否以及如何在宫内/产前和/或出生后通过牛奶或母体唾液传播。由于Prion状态和转移的性质不确定，我们将使用几种方法来检测CWD Prion--包括直接免疫分析、系列蛋白质错折叠循环扩增(SPMCA)和转基因小鼠生物检测。这项工作的目标是确定CWD Pron从母亲转移到子代的最重要的途径，从而全面了解垂直Pron传递的机制。

DESCRIPTION (provided by applicant): Chronic wasting disease (CWD) is an emergent, efficiently transmitted, fatal prion disease of cervids (deer, elk, moose) that is now identified in 17 states, 2 Canadian provinces and 1 Asian country. Epidemiological studies in deer suggest that CWD is transmitted horizontally, yet surprisingly little is known about its potential vertical transmission. The question of whether and how CWD, and prions overall, are transmitted from mother to offspring forms the basis for this proposal. We propose to address two specific aims to assess whether vertical/maternal transmission may explain in large part the efficient spread of CWD in nature by employing a newly developed small cervid model of CWD infection in Reeve's muntjac deer, which are readily housed and bred in indoor facilities. We will employ CWD- infected pregnant female muntjac deer and their offspring to determine whether and how infectious CWD prions are transmitted in utero/prenatally and/or postnatally via milk or maternal saliva. Due to uncertainties regarding the nature of prion state and transfer, we will use several assays to detect CWD prions--including direct immunoassays, serial protein misfolding cyclic amplification (sPMCA) and transgenic mouse bioassay. The goal of this work is to determine the most significant pathway whereby CWD prions are transferred from mother to offspring, and thereby to gain insight into the mechanisms of vertical prion transmission overall.