Krüger Dominique, Thomzig Achim, Lenz Gudrun, Kampf Kristin, McBride Patricia, Beekes Michael
Robert Koch-Institute, P24-Transmissible Spongiform Encephalopathies, Nordufer 20, D-13353 Berlin, Germany.
Vet Res. 2009 Jan-Feb;40(1):4. doi: 10.1051/vetres:2008042. Epub 2008 Oct 3.
Shedding of prions via faeces may be involved in the transmission of contagious prion diseases. Here, we fed hamsters 10mg of 263K scrapie brain homogenate and examined the faecal excretion of disease-associated prion protein (PrP(TSE)) during the course of infection. The intestinal fate of ingested PrP(TSE) was further investigated by monitoring the deposition of the protein in components of the gut wall using immunohistochemistry and paraffin-embedded tissue (PET) blotting. Western blotting of faecal extracts showed shedding of PrP(TSE) in the excrement at 24-72 h post infection (hpi), but not at 0-24 hpi or at later preclinical or clinical time points. About 5% of the ingested PrP(TSE) were excreted via the faeces. However, the bulk of PrP(TSE) was cleared from the alimentary canal, most probably by degradation, while an indiscernible proportion of the inoculum triggered intestinal infection. Components of the gut-associated lymphoid tissue (GALT) and the enteric nervous system (ENS) showed progressing accumulation of PrP(TSE) from 30 days post infection (dpi) and 60 dpi, respectively. At the clinical stage of disease, substantial deposits of PrP(TSE) were found in the GALT in close vicinity to the intestinal lumen. Despite an apparent possibility of shedding from Peyer's patches that may involve the follicle-associated epithelium (FAE), only small amounts of PrP(TSE) were detected in faeces from clinically infected animals by serial protein misfolding cyclic amplification (sPMCA). Although excrement may thus provide a vehicle for the release of endogenously formed PrP(TSE), intestinal clearance mechanisms seem to partially counteract such a mode of prion dissemination.
朊病毒通过粪便排出可能与传染性朊病毒疾病的传播有关。在此，我们给仓鼠喂食10毫克263K羊瘙痒病脑匀浆，并在感染过程中检测与疾病相关的朊病毒蛋白（PrP(TSE)）的粪便排泄情况。通过免疫组织化学和石蜡包埋组织（PET）印迹法监测肠道壁各成分中该蛋白的沉积情况，进一步研究摄入的PrP(TSE)在肠道内的去向。粪便提取物的蛋白质印迹分析显示，感染后24 - 72小时（hpi）粪便中有PrP(TSE)排出，但在0 - 24 hpi或后期临床前或临床时间点则没有。约5%摄入的PrP(TSE)通过粪便排出。然而，大部分PrP(TSE)从消化道清除，很可能是通过降解，而只有难以察觉比例的接种物引发肠道感染。肠道相关淋巴组织（GALT）和肠神经系统（ENS）的成分分别在感染后30天（dpi）和60 dpi时显示PrP(TSE)的积累逐渐增加。在疾病的临床阶段，在紧邻肠腔的GALT中发现了大量PrP(TSE)沉积。尽管明显有可能从派尔集合淋巴结排出，这可能涉及滤泡相关上皮（FAE），但通过连续蛋白质错误折叠循环扩增（sPMCA）在临床感染动物的粪便中仅检测到少量PrP(TSE)。因此，尽管粪便可能为内源性形成的PrP(TSE)的释放提供一种载体，但肠道清除机制似乎部分抵消了这种朊病毒传播方式。
