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Detection and tissue destribution of CWD and BSE PrPSc

CWD 和 BSE PrPSc 的检测和组织分布

基本信息

批准号：
7934048
负责人：
CLAUDIO SOTO
金额：
$ 31.28万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
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/7934048
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 Classification 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 Pathogenesis 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

项目摘要

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）是一组影响人类和动物的致命疾病