Analyois of infectivity in the blood from patients with prion disease

朊病毒病患者血液感染性分析

基本信息

批准号：
11557046
负责人：
MURAMOTO Tamaki
金额：
$ 8.38万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557046/
关键词：
Creutzfeldt-Jakob disease bioassay follicular dendritic cells blood knock-in mouse prions 感染性プリオン

项目摘要

It is important to know whether the blood of a patient with Creuzfeldt-Jakob disease (CJD) is infectious or not. In fact, United Kingdom gave up to make the blood-derived products using the blood samples in United Kingdom because patient with variant CJD have extraneuronal abnormal prion protein (PrP^<Sc>). These accumulations were observed in the follicular dendritic cells (FDC) before the onset of variant CJD. It is an urgent issue to establish a sensitive bioassay system, because bovine spongiform encephalopathy is now appeared in almost all European countries, and even in Japan in 2001. Previous bioassay system, which is based on the intracerebral inoculation, showed a high sensitivity to detect infectivity of 10^<-7> diluted samples but took a long time (about 2 years) to detect the onset of disease. With FDC assay, the accumulated PrP^<Sc> consisted of recombinant PrP, but not of the inoculated human PrP. These accumulations were detectable in the spleens of all mice examined 30 days post-inoculation. Infectivity of the spleen was also evident. The FDC bioassay takes a short incubation time and shows a high sensitivity to detect the infectivity even in 10^<-7> diluted samples. This bioassay is also available to detect variant CJD prions. Therefore, we established a rapid and sensitive bioassay method for human prions. This model should facilitate the prevention of infectious prion diseases.

重要的是要知道Creuzfeldt-Jakob病（CJD）患者的血液是否具有感染性。实际上，英国放弃了使用英国的血液样本制作血液衍生的产品，因为患有变异CJD的患者具有外交异常prion蛋白（PRP^<sc>）。在变体CJD发作之前，在卵泡树突状细胞（FDC）中观察到这些积累。建立一个敏感的生物测定系统是一个紧迫的问题，因为牛海绵状脑病现在几乎出现在所有欧洲国家，甚至在2001年的日本。基于脑内接种的先前的生物测定系统，表现出很高的敏感性，可检测到10^<-7>稀释的样品（大约两年）的敏感性（大约两年）（大约两年）。使用FDC分析，累积的PRP^<sc>由重组PRP组成，但不包括接种的人PRP。这些累积在接种后30天检查的所有小鼠的脾脏中均可检测到。脾脏的感染性也很明显。 FDC生物测定时间短，即使在10^<-7>稀释的样品中，也显示出高灵敏度以检测感染力。该生物测定也可用于检测变体CJD Prions。因此，我们建立了一种快速而敏感的生物测定方法，用于人类王室。该模型应促进预防感染性毒疾病。