Mother to Offspring Transmission of Chronic Wasting Disease

描述（由申请人提供）：慢性消耗性疾病（CWD）是一种紧急的，有效传播的，致命的动物（鹿，麋鹿，驼鹿）朊病毒疾病，目前在17个州，2个加拿大省和1个亚洲国家被发现。鹿的流行病学研究表明，CWD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。CWD和朊病毒是否以及如何从母体传播给后代的问题构成了这一建议的基础。我们提出了两个具体的目标，即通过在易于在室内设施中饲养和繁殖的Reeve’s munjac鹿中采用新开发的CWD感染小型宫颈模型，评估垂直/母源传播是否可以在很大程度上解释CWD在自然界的有效传播。我们将使用感染CWD的怀孕雌性麂鹿及其后代来确定传染性CWD朊病毒是否以及如何在子宫/产前和/或产后通过乳汁或母体唾液传播。由于朊病毒状态和转移性质的不确定性，我们将使用几种检测方法来检测CWD朊病毒，包括直接免疫测定、序列蛋白错误折叠循环扩增（sPMCA）和转基因小鼠生物测定。这项工作的目的是确定CWD朊病毒从母体转移到后代的最重要途径，从而全面了解朊病毒垂直传播的机制。

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.