Detection of Prions

朊病毒检测

• 批准号: 7964733
• 负责人: BYRON CAUGHEY
• 金额: $ 75.83万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 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/7964733
• 关键词: Agriculture; Biological Assay; Bovine Spongiform Encephalopathy; Brain; Cerebrospinal Fluid; Cerebrum; Chronic Wasting Disease; Clinic; Conversion disorder; Creutzfeldt-Jakob Syndrome; Detection; Development; Diagnosis; Diagnostic tests; Disease; Hamsters; Human; Infection; Medical; Methods; Neurodegenerative Disorders; Prion Diseases; Prions; Protein Isoforms; Sampling; Scrapie; Sheep; Testing; Time; Variant; base; brain tissue; interest; polymerization; pre-clinical; prion seeds

The pathological isoform of the prion protein (PrPres) can serve as a marker for prion diseases, but more practical tests are needed for preclinical diagnosis and sensitive detection of many prion infections. Previously we showed that the quaking-induced conversion (QuIC) assay can detect sub-femtogram levels of PrPres in scrapie-infected hamster brain tissue and distinguish cerebral spinal fluid (CSF) samples from normal and scrapie-infected hamsters. During FY2009, we adapted the QuIC reaction to prion diseases of medical and agricultural interest: human variant Creutzfeldt-Jakob disease (vCJD) and sheep scrapie. Prion-positive and negative brain homogenate samples from humans and sheep were discriminated within 1-2 days with a sensitivity of 10-100 femtograms PrPres. More importantly, in as little as 32h we were able to distinguish CSF samples from scrapie-infected and uninfected sheep. This is the first time that PrPres is detected in scrapie positive derived CSF. This new method enables the relatively rapid and sensitive detection of human CJD and sheep scrapie PrPres and may facilitate the development of practical preclinical diagnostic tests.

prion蛋白（PRPRES）的病理同工型可以作为prion疾病的标志物，但是临床前诊断和对许多prion感染的敏感检测需要更多的实际检测。以前，我们表明，质量诱导的转化率（QUIC）可以检测到刮刀感染的仓鼠脑组织中的PRPRES，并区分脑脊髓液（CSF）样品与正常和草皮症感染的仓鼠。 在2009财年期间，我们对医学和农业兴趣的政治疾病的反应进行了调整：人类变体C​​reutzfeldt-Jakob病（VCJD）和绵羊crap。 来自人类和绵羊的Prion阳性和负脑匀浆样品在1-2天内被歧视，灵敏度为10-100 femtograms Prpres。 更重要的是，在短短32H中，我们能够将CSF样品与受生物的感染和未感染的绵羊区分开。 这是第一次在crapie阳性派生的CSF中检测到Prpres。 这种新方法可以对人CJD和绵羊crapie Prpres进行相对较快和敏感的检测，并可能促进实用的临床前诊断测试的发展。