[转移贴]PLoS Pathogens：朊病毒蛋白研究进展

cao1976

原贴由wwwkkk83发表于 2008-9-2 17:56
http://biosky.haotui.com/thread-6292-1-9.html

朊病毒是一种只含有蛋白质成分的病毒，可引起羊瘙痒症和疯牛病等许多神经性疾病。

近日来自法国食品安全管理局的研究小组，鉴定出朊病毒蛋白的一个新特性，这一特性导致朊病毒能引起不同寻常的羊瘙痒病。这一研究论文8月29日发表在PLoS Pathogens上面，这一研究结果将为阮病毒种间传播的多样性特征提供新的研究思路。

朊病毒感染导致牛患海绵样脑病（BSE）的种群间传播机制至今还未明确，这种病毒还可通过牛肉食源性传播路径造成流行。典型的牛海绵样脑病俗称疯牛病，经食源传播的朊病毒会导致人患克雅氏病，对于克雅氏病暂无有效的治疗手段，通常导致人类产生退行性的神经障碍症状。科学家们发现朊病毒的中间传播机制可能与中间宿主有关，中间宿主包括羊，这些通常散发非典型的海绵样脑病，称为L-type BSE。

研究人员通过对朊病毒中一种具有抗蛋白酶活性的酶（protease-resistant prion protein ，PrPres）分子结构进行分析，发现引发羊瘙痒病与牛海绵样脑病的朊病毒蛋白间的区别。研究者将三种朊病毒（引起牛海绵样脑病的朊病毒，L-type型牛海绵样脑病朊病毒和羊瘙痒病朊病毒）分别感染转基因小鼠，结果转基因小鼠的大脑过度表达羊瘙痒病朊病毒蛋白。从感染了上述三种朊病毒的小鼠脑内抽取PrPres。结果发现，感染羊瘙痒病肮蛋白的动物发现有CH1641样的病例， CH1641病例的PrPres与L-type BSE和典型BSE的PrPres酶具有相似的分子特征。

在CH1641样的羊瘙痒病例中，阮病毒蛋白的分子结构特征与L-type型接近，而与典型的BSE结构有较大差异。但是，在4个CH1641羊瘙痒病例中，分离的朊病毒蛋白羧基端发生了病理性变化，而在典型的BSE阮病毒蛋白和L-type阮病毒蛋白里没有发现有类似的情况，这就表明，羊瘙痒病朊病毒不是从BSE朊病毒演化而成。

原始出处：PLoS Pathog 4(8): e1000137. doi:10.1371/journal.ppat.1000137

A C-Terminal Protease-Resistant Prion Fragment Distinguishes Ovine “CH1641-Like” Scrapie from Bovine Classical and L-Type BSE in Ovine Transgenic Mice

Thierry Baron*, Anna Bencsik, Johann Vulin, Anne-Ga?lle Biacabe, Eric Morignat, Jérémy Verchere, Dominique Betemps

AAbstract

The protease-resistant prion protein (PrPres) of a few natural scrapie isolates identified in sheep, reminiscent of the experimental isolate CH1641 derived from a British natural scrapie case, showed partial molecular similarities to ovine bovine spongiform encephalopathy (BSE). Recent discovery of an atypical form of BSE in cattle, L-type BSE or BASE, suggests that also this form of BSE might have been transmitted to sheep. We studied by Western blot the molecular features of PrPres in four “CH1641-like” natural scrapie isolates after transmission in an ovine transgenic model (TgOvPrP4), to see if “CH1641-like” isolates might be linked to L-type BSE. We found less diglycosylated PrPres than in classical BSE, but similar glycoform proportions and apparent molecular masses of the usual PrPres form (PrPres #1) to L-type BSE. However, the “CH1641-like” isolates differed from both L-type and classical BSE by an abundant, C-terminally cleaved PrPres product (PrPres #2) specifically recognised by a C-terminal antibody (SAF84). Differential immunoprecipitation of PrPres #1 and PrPres #2 resulted in enrichment in PrPres #2, and demonstrated the presence of mono- and diglycosylated PrPres products. PrPres #2 could not be obtained from several experimental scrapie sources (SSBP1, 79A, Chandler, C506M3) in TgOvPrP4 mice, but was identified in the 87V scrapie strain and, in lower and variable proportions, in 5 of 5 natural scrapie isolates with different molecular features to CH1641. PrPres #2 identification provides an additional method for the molecular discrimination of prion strains, and demonstrates differences between “CH1641-like” ovine scrapie and bovine L-type BSE transmitted in an ovine transgenic mouse model.

http://www.plospathogens.org/art ... ournal.ppat.1000137