Project 3B: Pathogenesis Transmission and Detection of Zoonotic Prion Diseases

项目摘要： 慢性消耗性疾病（CWD）是一种突发的、高度传播的、地理上扩展的朊病毒 野生和圈养鹿的疾病。慢性消耗病在朊病毒疾病中是独特的，因为它容易传染， 环境持久性其不断扩大的地理范围，加上日益增加的运输， 动物和动物产品，预示着它的持续扩张和多样化。人畜共患病的可能性 对慢性消耗病的了解仍然很少。慢性消耗病流行区将鹿科动物与牲畜物种和人类联系在一起， 造成明显的人畜共患病风险，随着时间的推移，风险将增加。虽然已知存在慢性消耗病菌株，但没有任何 已知这些菌株的人畜共患病潜力。我们的申请人小组的工作表明，CWD- 受感染的鹿科动物不断地将朊病毒释放到环境中， 一些因素可以影响混合物中优势菌株的出现。识别人畜共患病的能力 CWD菌株的潜力是减轻CWD传播风险的关键。关于功的中心假设 这里描述的是CWD菌株由于宿主和环境的组合而不断进化 因素我们将通过以下方式检验这一假设：i）确定CWD菌株在环境中的进化和人畜共患影响， 本地鹿科物种; ii）利用我们独特的动物资源，专业知识，以及体内和体外 评估改变CWD菌株选择和进化的环境因素的方法，以及iii）评估 CWD菌株的人畜共患病潜力，通过体外扩增试验的互补组合， 动物传播研究这一结果将为这种新出现的传染性朊病毒提供新的信息 疾病及其对人类和其他物种构成的风险。

Project Summary: Chronic wasting disease (CWD) is an emergent, highly transmissible, geographically expanding, prion disease of both wild and captive cervids. CWD is unique among prion diseases in its facile contagion and environmental persistence. Its expanding geographical range, combined with the increasing transport of animals and animal products, portend its continued expansion and diversification. The zoonotic potential of CWD remains poorly understood. CWD endemic areas interface cervids with livestock species and humans, posing obvious zoonotic risks that over time will increase. While it is known that strains of CWD exist, nothing is known about the zoonotic potential of these strains. Work from our applicant group has shown that CWD- infected cervids continually shed prions into the environment and that previously unrecognized environmental factors can influence the emergence of a dominant strain from a mixture. The ability to recognize the zoonotic potential of CWD strains is central to mitigating CWD transmission risk. The central hypothesis for work described here is that CWD strains evolve continuously due to a combination of both host and environmental factors. We will test this hypothesis by: i) determining the evolution and zoonotic impact of CWD strains in the native cervid species; ii) leveraging our unique animal resources, expertise, and in vivo & in vitro methodologies to assess environmental factors that alter CWD strain selection and evolution and iii) evaluate zoonotic potential of CWD strains by a complementary combination of in vitro amplification assays and animal transmission studies. The results will provide new information about this emergent transmissible prion disease and the risk it poses to humans and other species.