Detection of Prions

朊病毒检测

• 批准号: 8555995
• 负责人: BYRON CAUGHEY
• 金额: $ 63.78万
• 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/8555995
• 关键词: Agriculture; Biological Assay; Bovine Spongiform Encephalopathy; Cerebrospinal Fluid; Chronic Wasting Disease; Clinic; Clinical; Creutzfeldt-Jakob Syndrome; Data; Detection; Diagnosis; Diagnostic; Disease; Hamsters; Human; Infection; Liquid substance; Neurodegenerative Disorders; Nose; Prion Diseases; Prions; Protein Isoforms; Sampling; Scrapie; Sensitivity and Specificity; Structure of mucous membrane of nose; Testing; Training; base; brain tissue; 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. During FY2012: 1) We trained and collaborated with human TSE surveillance groups to evaluate the utility of our previously developed RT-QuIC assay for the detection and diagnosis of human sporadic Creutzfeldt-Jakob disease. The data showed that RT-QuIC sensitively detects prion seeding activity in brain tissue from a wide variety of human CJD cases. Moreover, when applied to clinical cerebrospinal fluid samples, RT-QuIC has better sensitivity and specificity than any prior diagnostic cerebrospinal fluid test. 2) We determined how early after prion inoculation that we could detect signs of infection in the cerebrospinal fluid of hamsters using RT-QuIC. 3) Having previously detected prion infectivity in the nasal fluids of scrapie-infected hamsters, we determined the effects of disturbing the nasal mucosa on the release of prion infectivity. The results showed major increases in infectious prion release with a nasotoxic treatment.

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。在2012财年：1）我们与人类TSE监视组进行了培训和合作，以评估我们先前开发的RT Quic测定法的实用性，用于检测和诊断人类零星的Creutzfeldt-Jakob病。 数据表明，RT Quic敏感地检测到来自各种人CJD病例的脑组织中的Prion播种活性。此外，当应用于临床脑脊液样品时，RT Quic具有比任何先前诊断性脑脊液测试的灵敏度和特异性更好。 2）我们确定了在prion接种后的早期，我们可以使用RT-QUIC检测仓鼠脑脊液中感染的迹象。 3）在先前检测到的抓仓鼠的鼻腔流体中的Prion感染性，我们确定了干扰鼻粘膜对prion感染性释放的影响。结果表明，通过鼻毒性治疗，传染性prion释放的大幅增加。