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

项目3B：人畜共患朊病毒病的发病机制、传播和检测

• 批准号: 10589836
• 负责人: Jason C Bartz
• 金额: $ 28.88万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589836
• 关键词: American; Animals; Area; Attention; Binding; Biological Assay; Body Fluids; Brain; Chronic Wasting Disease; Deer; Detection; Endemic Diseases; Environment; Environmental Impact; Environmental Risk Factor; Evolution; Gene Targeting; Generations; Genotype; Geography; Health; Human; In Vitro; Infection; Integration Host Factors; Laboratories; Lesion; Livestock; Lymphoid Tissue; Methodology; Methods; Molecular Conformation; Mus; Pathogenesis; Peptide Hydrolases; PrP; PrPSc Proteins; Prion Diseases; Prions; Property; Recombinants; Resistance; Risk; Risk Assessment; Role; Scandinavia; Scandinavian; Soil; Surface; Tail; Testing; Time; Tissues; Transgenic Organisms; Variant; Weather; Western Blotting; Work; Zoonoses; animal resource; cervid; conformer; contagion; cross-species transmission; detection method; disease transmission; in vivo; neural; particle; prototype; risk prediction; transmission process; zoonotic spillover

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.

项目摘要： 慢性浪费疾病（CWD）是一种新兴的，高度传播的，地理位置扩展的 野生和圈养子宫颈的疾病。 CWD在其轻松传染中是独一无二的 环境持久性。它不断扩大的地理范围，加上越来越多的运输 动物和动物产品预示着其持续的扩展和多样化。人畜共患潜力 CWD仍然很了解。 CWD地方性地区与牲畜物种和人类的界面界面， 随着时间的流逝会带来明显的人畜共患风险。虽然知道CWD菌株存在，但没有 关于这些菌株的人畜共患潜力已知。我们申请人组的工作表明，CWD- 感染的子宫颈不断地将王室浸入环境中，而以前未被认可的环境 因素可以影响混合物的主要菌株出现。识别人畜共患病的能力 CWD菌株的潜力对于减轻CWD传输风险至关重要。工作的中心假设 此处描述的是，由于宿主和环境的结合，CWD菌株不断发展 因素。我们将通过：i）确定CWD菌株在 本地子宫颈物种； 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论以及III）评估 CWD菌株的人畜共患潜力，通过体外扩增测定法的互补组合和 动物传播研究。结果将提供有关这种新兴传播的prion的新信息 疾病及其对人类和其他物种的风险。