Detection and tissue destribution of CWD and BSE PrPSc

CWD 和 BSE PrPSc 的检测和组织分布

• 批准号: 8129596
• 负责人: CLAUDIO SOTO
• 金额: $ 32.03万
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8129596
• 关键词: Address; Affect; Animal Diseases; Animals; Area; Basic Science; Biochemical; Biological; Biological Assay; Bladder; Blinded; Blood; Blood specimen; Bovine Spongiform Encephalopathy; Brain; Brain Stem; Buffers; Cattle; Cell Surface Proteins; Characteristics; Chronic Wasting Disease; Clinical; Creutzfeldt-Jakob Syndrome; Data; Deer; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Drug or chemical Tissue Distribution; Early Diagnosis; Environment; Equilibrium; Exhibits; Feces; Food Chain; Glycoproteins; Goals; Hamsters; Head; Health; Heart; Human; In Vitro; Incubated; Infection; Infectious Agent; Intestines; Kidney; Liquid substance; Liver; Lung; Lymphoid; Measures; Methodology; Methods; Mus; Muscle; Names; Nervous system structure; Neuraxis; Normal Cell; North America; Organ; Outcome; Peripheral; Peripheral Nerves; Phase; Poaceae; PrP; PrPSc Proteins; Prevalence; Principal Investigator; Prion Diseases; Prions; Procedures; Process; Property; Protein Isoforms; Proteins; Protocols documentation; Reaction; Relative (related person); Replication-Associated Process; Reporting; Research; Risk; Risk Assessment; Route; Saliva; Sampling; Scrapie; Sensitivity and Specificity; Sheep; Skin; Soil; Sonication; Source; Speed; Spinal Cord; Spleen; Staging; Stomach; Surrogate Markers; Surveys; Technology; Testing; Time; Time Study; Tissues; Transgenic Mice; Tube; Urine; Western Blotting; animal tissue; assay development; base; cervid; experience; in vivo; mouse model; numb protein; prevent; process optimization; programs; protein misfolding cyclic amplification; research study; single molecule; soil sampling; transmission process

Transmissible spongiform encephalopathies (TSEs) are a group of fatal diseases affecting humans and animals, including Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and chronic wasting disease (CWD) in cervids. Prions are the infectious agent associated to TSEs, which appears to be composed exclusively by a misfolded version of the normal prion protein (termed PrPSc), and the disease is transmitted by propagation of the misfolding from the disease associated isoform to the normal host protein (termed PrPc). We have recently described a procedure to induce the conversion of PrPc into PrPSc in vitro starting with minute quantities of brain PrPSc. This procedure, named Protein Misfolding Cyclic Amplification (PMCA) mimics the process of prion replication in vivo, but at an accelerated speed resulting in an exponential amplification of the initial amount of PrPSc. The major goals of this project are to study the replication of CWD and BSE prions in vitro, evaluate tissue distributions of infectious protein, enlighten the routes of transmission and develop a diagnostic assay for CWD and BSE infected animals. In specific aim 1 we will optimize the PMCA technology for efficient high-sensitivity detection of cattle and deer PrPSc; Specific aim 2 proposes to use the technology to evaluate the tissue distribution of the infectious agent at different times during the incubation period in cattle and deer infected animals; In specific aim 3 we will to study the routes of transmission of CWD by analyzing source of materials (such as soil and grass) from animals' natural environment and excretory fluids (feces, urine, saliva); Finally specific aim 4 will attempt to develop a sensitive diagnostic test for BSE and CWD using blood or urine samples. This project offers a balanced combination between basic science mechanistic studies aimed to understand the most relevant scientific problems in the field of zoonotic prion disease and applied studies to resolve the main practical problem associated to these diseases, which is the lack of a highly-sensitive pre-symptomatic diagnosis to limit the spreading of these incurable illnesses.

传染性海绵状脑病（TSE）是一组影响人类的致命疾病， 动物，包括人类的克雅氏病（CJD），羊瘙痒症，牛海绵状 牛的脑病（BSE）和鹿的慢性消耗病（CWD）。朊病毒是传染性的 与TSEs相关的代理人，似乎完全由正常的错误折叠版本组成 朊病毒蛋白（称为PrPSc），这种疾病是通过传播的错误折叠从 疾病相关同种型转化为正常宿主蛋白（称为PrPc）。我们最近描述了一个 从微量脑PrPSc开始体外诱导PrPc转化为PrPSc的程序。 这个过程，称为蛋白质错误折叠循环扩增（PMCA）模拟朊病毒的过程 在体内复制，但以加速的速度导致初始量的指数扩增 的PrPSc。本项目的主要目的是研究慢性消耗病和疯牛病朊病毒在体外的复制， 评估感染性蛋白的组织分布，揭示传播途径，并制定 CWD和BSE感染动物的诊断试验。在具体目标1中，我们将优化PMCA 牛和鹿PrPSc的高效高灵敏度检测技术;具体目标2建议使用 在孵育期间不同时间评估感染原组织分布的技术 在特定目标3中，我们将研究 通过分析动物自然环境中的物质来源（如土壤和草）， 排泄液（粪便、尿液、唾液）;最后，具体目标4将尝试开发一种灵敏的诊断测试 检测疯牛病和慢性消耗病该项目提供了一个平衡的组合之间的基本 科学机制研究旨在了解该领域最相关的科学问题， 人畜共患朊病毒病和应用研究，以解决与这些相关的主要实际问题 疾病，这是缺乏一个高度敏感的症状前诊断，以限制这些传播 不治之症