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Pathogenesis of BSE and highly sensitive isolation of BSE agent

BSE 的发病机制和 BSE 试剂的高灵敏分离

基本信息

批准号：
17380174
负责人：
ONODERA TAKASBI
金额：
$ 9.54万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17380174/
关键词：
prion BSE scrapie food safety gene

项目摘要

The chain reaction of BSE epidemics in the UK and Europe and subsequent emergence of vCJD in young adults and teenagers have raised concerns and highlighted the importance of risk assessment in the food chain. Recently, several highly sensitive methods for detecting priors have been developed. Representative of these is PMCA.Originally developed by Claudio Soto and his colleagues, PMCA has been a hot topic of debate in prion meetings all over the world. A broad spectrum of PrP^Sc species have now been successfully amplified using PMCA, including CWD, mouse-adapted scrapie, and BSE. Studies with human sporadic and variant CJD cases show that PMCA amplification efficiency is tightly controlled by the PrP^C substrate genotype at codon 129. PMCA appears to overcome the species barrier encountered during cross-species transmission more rapidly than in vivo. By "forcing" the technique with lower dilutions of the PrP^Sc seed and more amplification rounds, mouse Chandler PrP^Sc can now convert hamster PrP^C or cervid PrP^C, a conversion that might be observable in vivo but only with extremely long incubation periods. Castilla J. showed that using PMCA, PrP^Sc was generated from the healthy brains of 11 different species, including bank voles, mice, cattle, humans, sheep and rabbits, generating a variety of electrophoretic profiles. PMCA was able to detect PrP^Sc in as little as 1 μL of blood from an asymptomatic prion-infected mouse. Given the increasing evidence of human to human transmission via blood products, scientists are waiting for PMCA to be incorporated into a reliable test with the ability to identify blood donors that are asymptomatic carriers. Further advances in amplification technology are to be expected and the replacement of PrP^C by recombinant PrP as a substrate as well as the use of intermittent shaking rather than sonication should circumvent some of the difficulties in the near future.

英国和欧洲疯牛病流行的连锁反应以及随后在年轻人和青少年中出现的vCJD引起了人们的关注，并突出了食物链风险评估的重要性。最近，已经开发了几种用于检测先验的高灵敏度方法。PMCA最初由Claudio Soto和他的同事开发，一直是世界各地朊病毒会议的热门话题。现在，广泛的PrP^Sc种类已被PMCA成功扩增，包括慢性消耗病、小鼠适应性羊瘙痒病和疯牛病。对人类散发性和变异型克雅氏病病例的研究表明，PMCA扩增效率受到密码子129处PrP^C底物基因型的严格控制。PMCA似乎克服跨物种传播过程中遇到的物种障碍比在体内更快。通过“强制”该技术使用较低稀释度的PrP^Sc种子和更多的扩增轮次，小鼠钱德勒PrP^Sc现在可以转化仓鼠PrP^C或鹿PrP^C，这种转化可能在体内可观察到，但只有在极长的孵育期内才能观察到。卡斯蒂利亚·J表明，使用PMCA，PrP^Sc是从11个不同物种的健康大脑中产生的，包括银行田鼠、小鼠、牛、人、绵羊和兔子，产生了各种电泳图谱。PMCA能够在无症状朊病毒感染小鼠的1 μL血液中检测出PrP^Sc。鉴于越来越多的证据表明，人与人之间通过血液制品传播，科学家们正在等待PMCA被纳入一个可靠的测试，以确定献血者是无症状的携带者。扩增技术的进一步发展是可以预期的，用重组PrP替代PrP^C作为底物，以及使用间歇振荡而不是超声处理，在不久的将来应该可以克服一些困难。