Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a new prion strain
Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a new prion strain
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DOI：
10.1074/jbc.m704597200
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发表时间：
2007-10-12
影响因子：
4.8
通讯作者：
Kitamoto, Tetsuyuki
中科院分区：
文献类型：
--
作者：
Kobayashi, Atsushi;Asano, Masahiro;Kitamoto, Tetsuyuki
人朊蛋白（PrP）基因多态性密码子129的基因型（蛋氨酸或缬氨酸）和PrP （PrPSc）异常异构体的型（1型或2型）是散发性克雅氏病（sCJD）临床病理表型的主要决定因素。本研究发现，将缬氨酸纯合性（129V/V）和2型PrPSc患者的sCJD朊病毒（sCJD- vv2朊病毒）传播给表达蛋氨酸纯合性（129M/M）的人PrP的小鼠，会产生介于1型和2型之间的异常PrPSc。在所有硬脑膜移植物相关的CJD病例中均可见到中间型PrPSc，有129M/M和斑块型PrP沉积（p-dCJD）。以129M/M或129V/V接种prp人源化小鼠时，p- djd朊病毒和sCJD-VV2朊病毒具有相似的传播性和神经病理学，PrPSc类型相同。这些结果提示，p- djd可能是由sCJD-VV2朊病毒的跨序列传播引起的。
The genotype ( methionine or valine) at polymorphic codon 129 of the human prion protein (PrP) gene and the type ( type 1 or type 2) of abnormal isoform of PrP ( PrPSc) are major determinants of the clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found that the transmission of sCJD prions from a patient with valine homozygosity (129V/V) and type 2 PrPSc (sCJD-VV2 prions) to mice expressing human PrP with methionine homozygosity (129M/M) generated unusual PrPSc intermediate in size between type 1 and type 2. The intermediate type PrPSc was seen in all examined dura mater graft-associated CJD cases with 129M/M and plaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prions exhibited similar transmissibility and neuropathology, and the identical type of PrPSc when inoculated into PrP-humanized mice with 129M/M or 129V/V. These findings suggest that p-dCJD could be caused by cross-sequence transmission of sCJD-VV2 prions.