Prion strain discrimination using luminescent conjugated polymers
Prion strain discrimination using luminescent conjugated polymers
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DOI：
10.1038/nmeth1131
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发表时间：
2007-12-01
期刊：
影响因子：
48
通讯作者：
Aguzzi, Adriano
中科院分区：
文献类型：
--
作者：
Sigurdson, Christina J.;Peter, K.;Aguzzi, Adriano
多株朊病毒的出现可能反映了PrPSc的构象变异性，PrPSc是细胞朊病毒蛋白PrPC的一种与疾病相关的聚集变体。在这里，我们使用发光共轭聚合物（LCP），它发出构象依赖的荧光光谱，用于表征朊病毒菌株。LCP反应性和发射光谱的大脑部分区分四个化学上不可区分的，连续小鼠传代朊病毒株来自羊瘙痒症，慢性消耗性疾病（CWD），牛海绵状脑病（BSE），和小鼠适应落基山实验室瘙痒症朊病毒。此外，使用LCP，我们区分了BSE和牛淀粉样海绵状脑病的现场分离株，并确定了朊病毒感染的鹿和羊的非嗜中性沉积物。我们发现，从化学上相同的重组PrP产生的具有不同形态的原纤维产生独特的LCP光谱，这表明光谱特征差异导致不同的超分子PrP结构。LCP可能有助于检测离散蛋白质聚集体之间的结构差异，并将蛋白质构象特征与疾病表型联系起来。
The occurrence of multiple strains of prions may reflect conformational variability of PrPSc, a disease-associated, aggregated variant of the cellular prion protein, PrPC. Here we used luminescent conjugated polymers (LCPs), which emit conformation-dependent fluorescence spectra, for characterizing prion strains. LCP reactivity and emission spectra of brain sections discriminated among four immunohistochemically indistinguishable, serially mouse-passaged prion strains derived from sheep scrapie, chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE), and mouse-adapted Rocky Mountain Laboratory scrapie prions. Furthermore, using LCPs we differentiated between field isolates of BSE and bovine amyloidotic spongiform encephalopathy, and identified noncongophilic deposits in prion-infected deer and sheep. We found that fibrils with distinct morphologies generated from chemically identical recombinant PrP yielded unique LCP spectra, suggesting that spectral characteristic differences resulted from distinct supramolecular PrP structures. LCPs may help to detect structural differences among discrete protein aggregates and to link protein conformational features with disease phenotypes.