Studies on the entry ports for the scrapie agent (prion)

动物普恩病毒病的主要感染原因被认为是口服被普恩病毒污染的东西。有证据表明肠道神经系统(ENS)和淋巴组织，尤其是肠道相关淋巴组织(GATL)参与了Pron经消化道的感染。为了阐明Prion的初始进入端口，我们将Prion接种到全身淋巴结和Peyer‘s斑块缺乏的ALY小鼠身上，通过不同的途径。Aly/Aly小鼠经颅接种对Prion易感，而经腹接种则表现出较低的敏感性。Aly/Aly小鼠经口给药完全抵抗，而Aly/Aly小鼠的野生型C57BL/6J小鼠在接种后307±7天对经口给药敏感，达到疾病的终末期。感染Prion的C57BL/6J小鼠的肠道和脾组织中甚至在暴露早期即可检测到Pron的感染性，而Pron免疫的Aly/Aly小鼠的肠道和脾组织中未检测到传染性。PrPSc仅在C57BL/6小鼠的肠道和脾中检测到，而在感染羊痒病的Aly/Aly小鼠的脾和肠道中未检测到PrPSc。野生型与Aly/Aly小鼠在肠道神经系统的组织结构上无明显差异。这些结果表明，不是ENS，而是GALT在口腔暴露后是普恩的主要进入端口。

Major cause of infection in animal prion diseases is thought to be consumption of prion-contaminated stuff orally. There is evidence that the enteric nerve system (ENS) and lymphoid tissues, especially gut-associated lymphoid tissues (GATL) is involved in the infection of prion via alimentary tract. To elucidate the initial entry port for prion, we inoculated prion to alympholasia (aly) mice that show a deficiency in the systemic lymph nodes and Peyer's patches with various route. The aly/aly mice was susceptible to prion by intra-cranial inoculation, however, they showed reduced susceptibility with intra-peritoneal inoculation. The aly/aly mice were completely resistant to with per os administration, while C57BL/6J mice, the wild type mice for aly/aly mice, were sensitive to per os administration as they got the terminal stage of disease 307±7 days post inoculation. The prion infectivities were detected in the intestine and spleen of prion-inoculated C57BL/6J mice even after the early stage of exposure, whereas no infectivity was detected from those tissues of prion-inoculated aly/aly mice. PrPSc also detected in the intestine and spleen only of C57BL/6 mice, however PrPSc was not detected in the spleen and intestine of aly/aly mice that was affected by scrapie with the intra-peritoneal inoculation. No apparent difference in the organization of enteric nerve system was found between wild type and aly/aly mice. These results indicate that not ENS but GALT acts as a primary entry port for prion after the oral exposure.