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.

了解克雅氏病 (CJD) 患者的血液是否具有传染性非常重要。事实上，由于变异型克雅氏病患者存在神经元外异常朊病毒蛋白（PrP^<Sc>），英国放弃使用英国的血液样本生产血液制品。在变异型克雅氏病发作之前，在滤泡树突状细胞 (FDC) 中观察到这些积累。建立灵敏的生物测定系统是一个紧迫的问题，因为现在几乎所有欧洲国家都出现了牛海绵状脑病，甚至在2001年的日本也出现了这种情况。以前的生物测定系统基于脑内接种，表现出很高的检测灵敏度10^-7稀释样本的感染性，但需要很长时间（约2年）才能检测到疾病的发作。通过FDC测定，积累的PrP ^ Sc 由重组PrP组成，但不由接种的人PrP组成。接种后 30 天检查的所有小鼠的脾脏中均可检测到这些积累。脾脏的感染性也很明显。 FDC生物测定需要很短的孵育时间并且即使在10^-7稀释的样品中也显示出检测感染性的高灵敏度。该生物测定还可用于检测变异克雅氏病朊病毒。因此，我们建立了一种快速、灵敏的人朊病毒生物测定方法。该模型应有助于预防传染性朊病毒疾病。