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.

项目总结： 慢性消耗性疾病(CWD)是一种突发的、高度传染性的、地理上扩展的普恩病毒 野生和圈养子宫颈的疾病。慢性萎缩性脑病在普恩病毒疾病中是独一无二的，因为它容易传染和 环境坚持不懈。它不断扩大的地理范围，加上不断增加的 动物和动物产品，预示着其继续扩张和多样化。人畜共患病的潜力 CWD仍然知之甚少。慢性萎缩性脑病流行地区将鹿类与牲畜物种和人类联系起来， 带来了明显的人畜共患病风险，随着时间的推移，这种风险将会增加。虽然CWD的菌株是已知的，但没有 已经知道这些菌株具有人畜共患病的潜力。我们申请组的工作表明，CWD- 受感染的宫颈不断地向环境中释放普恩病毒，而此前未被识别的环境 各种因素可以影响从混合物中出现优势菌株。识别人畜共患病的能力 CWD毒株的潜力是降低CWD传播风险的核心。关于工作的中心假设 这里描述的是CWD菌株由于宿主和环境的结合而不断进化 各种因素。我们将通过以下方式检验这一假设：i)确定CWD菌株在中国的进化和人畜影响 本地鹿类；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和III)评估 体外扩增和联合检测CWD菌株的人畜共患病潜力 动物传播学研究。这一结果将提供关于这种新出现的可传播的普恩病毒的新信息 疾病及其对人类和其他物种构成的风险。