CWD Prion Shedding and Environmental Contamination: Role in Transmission and Zoonotic Potential

CWD 朊病毒脱落和环境污染：在传播和人畜共患潜力中的作用

• 批准号: 9920665
• 负责人: EDWARD Arthur HOOVER
• 金额: $ 61.1万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2022-03-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9920665
• 关键词: Affect; Affinity; Animals; Area; Binding; Biological; Biological Assay; Biological Availability; Cattle; Chronic Wasting Disease; Collaborations; Complex; Consumption; Deer; Detection; Domestic Animals; Endemic Diseases; Environment; Environmental Exposure; Environmental Pollution; Excretory function; Exposure to; Geography; Goals; Human; In Vitro; Infection; Liquid substance; Livestock; Maintenance; Metals; Methods; Particulate; Pathogenesis; Plants; Prion Diseases; Prions; Process; Protocols documentation; Research; Risk; Rodent; Rodent Model; Role; Route; Science; Sheep; Soil; Surface; Techniques; Testing; Work; Zoonoses; animal facility; cervid; disease transmission; in vitro Assay; in vivo; insight; transmission process

PROJECT SUMMARY Chronic wasting disease (CWD) is an emergent highly transmissible prion disease of cervids (deer, elk). The zoonotic threat to domestic animal species and humans CWD represents remains poorly understood. A prominent feature of CWD is abundant shedding of prions in secretions and excretions, thereby facilitating exposure of animals and humans by either direct and/or indirect/environmental contact. Prions avidly bind to many surfaces, including plant, metal, and soil constituents, and appear to remain infectious, thus leading to cumulative persistence in the environment. However, little is known about the impact and zoonotic transmission risk represented by shed CWD prions. The long-term goal of this research is to understand the prion/environment interface and thereby develop effective mitigation strategies to reduce both the spread of CWD and the direct and indirect exposure to humans. The central hypothesis for this work is that the robust transmission of CWD reflects a unique convergence of florid prion shedding and avid prion binding to soil constituents, thereby enhancing environmental persistence and bioavailability. To test this hypothesis we propose the following specific aims: Aim 1 will determine the amplitude and temporal shedding profile of CWD prions from the natural cervid host. Almost surely, shedding of prions into the environment contributes to long-term maintenance of CWD infection in natural settings. We will longitudinally quantify the level of prions in excreta of CWD infected deer to determine the magnitude of the CWD prion load introduced into the environment by infected animals. Aim 2 will define the distribution of CWD prions in simulated and naturally contaminated environments. While prions have been shown to bind to soil and remain infectious, to date means to directly detect CWD prions in the environment are still lacking. The results will determine where CWD prions are located in the environment. Aim 3 will define the factors that control prion bioavailability in the environment. It is not known how this avid binding affects prion stability, survival, and infectivity in the presence of environmental degradation processes. The results of this aim will determine whether (or not) soil binding enhances CWD transmission. These studies will: (1) Enable more targeted strategies to mitigate the spread and potential risks of this emerging uncontrolled prion disease in free-ranging animals; (2) Provide insight regarding the interfaces wherein inter-species CWD prion transmission could occur; and (3) Determine the practical consequences of prion binding to environmental constituents.

项目摘要 慢性消耗病（CWD）是一种新发的高度传染性鹿朊病毒病 (deer、麋鹿）。人畜共患病对家畜物种和人类的威胁， 仍然知之甚少。慢性消耗病的一个显著特征是朊病毒的大量脱落， 分泌物和排泄物，从而促进动物和人类通过直接接触 和/或间接/环境接触。朊病毒可以与许多表面结合，包括植物， 金属和土壤成分，并似乎保持感染性，从而导致累积 在环境中的持久性。然而，对影响和人畜共患病知之甚少， 传播风险表现为脱落的慢性消耗病朊病毒。这项研究的长期目标是 了解朊病毒/环境界面，从而制定有效的缓解策略 以减少慢性消耗病的传播以及对人类的直接和间接接触。中央 这项工作的假设是，CWD的稳健传播反映了一种独特的收敛性， 华丽的朊病毒脱落和贪婪的朊病毒结合到土壤成分，从而提高 环境持久性和生物利用度。为了验证这一假设，我们提出以下建议 具体目标：目标1将确定慢性消耗病朊病毒的幅度和时间脱落概况 从自然的鹿科宿主身上分离出来几乎可以肯定的是，朊病毒进入环境有助于 长期维持慢性消耗病感染的自然环境。我们将纵向量化 感染CWD的鹿排泄物中朊病毒的水平，以确定CWD朊病毒的大小 由受感染动物引入环境的负荷。目标2将定义 模拟和自然污染环境中的慢性消耗病朊病毒。虽然朊病毒一直是 显示与土壤结合并保持传染性，迄今为止，直接检测CWD朊病毒的方法是 环境仍然缺乏。结果将确定慢性消耗病朊病毒位于 环境目标3将定义控制朊病毒在环境中生物利用度的因素。它 目前尚不清楚这种亲合性结合如何影响朊病毒的稳定性、存活和感染性， 环境退化过程。这一目标的结果将决定是否（或不） 土壤结合增强了CWD的传播。 这些研究将：（1）使更有针对性的战略，以减轻蔓延和潜在的风险 这种新出现的不受控制的朊病毒疾病在自由放养的动物;（2）提供洞察力 关于物种间慢性消耗病朊病毒传播可能发生的界面;以及（3） 确定朊病毒与环境成分结合的实际后果。