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

动物朊病毒疾病感染的主要原因被认为是口服被朊病毒污染的物质。有证据表明，肠神经系统（ENS）和淋巴组织，特别是肠相关淋巴组织（GATL）参与了朊病毒经消化道感染。为了阐明朊病毒的初始进入口岸，我们以不同途径将朊病毒接种到全身淋巴结和Peyer's斑块缺乏的淋巴缺陷小鼠。脑内接种的aly/aly小鼠对朊病毒敏感，腹膜内接种的小鼠对朊病毒的敏感性降低。aly/aly小鼠完全耐药，而aly/aly野生型小鼠C57BL/6J小鼠在接种后307±7 d达到疾病终末期，对per os敏感。在C57BL/6J小鼠的肠道和脾脏中，即使在早期暴露后也能检测到朊病毒的感染性，而在aly/aly小鼠的肠道和脾脏中未检测到朊病毒的感染性。PrPSc仅在C57BL/6小鼠的肠道和脾脏中检测到，而在腹腔接种的aly/aly小鼠的脾脏和肠道中未检测到PrPSc。野生型与aly/aly小鼠肠道神经系统组织无明显差异。这些结果表明，在口腔接触后，朊病毒的主要入口不是ENS，而是GALT。

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.