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

瘙痒病因子（朊病毒）进入端口的研究

• 批准号: 12660268
• 负责人: HORIUCHI Motohiro
• 金额: $ 0.7万
• 依托单位: Obihiro University of Agriculture and Veterinary Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12660268/
• 关键词: prion; scrapie; PrP; ALY; Gut-associated lymphoid tissue; Follicular dendritic cell; BSE; 消化管付髄リンパ装置; ALYマウス; バイエル氏板; 伝達性海綿状脳症

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.

感染动物朊病毒疾病的主要原因被认为是口服朊病毒污染的食物。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）参与了朊病毒通过消化道的感染。为了阐明朊病毒的初始进入端口，我们用不同途径将朊病毒接种到表现出全身淋巴结和派尔集合淋巴结缺陷的淋巴球麻痹症（aly）小鼠。aly/aly小鼠对脑内接种的朊病毒敏感，而腹腔内接种的小鼠对朊病毒的敏感性降低。aly/aly小鼠对口服给药完全耐受，而aly/aly小鼠的野生型小鼠C57 BL/6 J小鼠对口服给药敏感，因为它们在接种后307±7天达到疾病的终末期。感染朊病毒的C57 BL/6 J小鼠的肠和脾中检测到朊病毒感染性，即使在暴露的早期阶段，而没有感染性检测到从这些组织的朊病毒接种的aly/aly小鼠。在C57 BL/6小鼠的肠和脾中也检测到PrPSc，而在感染瘙痒病的aly/aly小鼠的脾和肠中则未检测到PrPSc。野生型小鼠和aly/aly小鼠肠神经系统的组织结构无明显差异。这些结果表明，不是ENS，而是GALT作为朊病毒经口暴露后的主要进入端口。

项目成果

Horiuchi, M., et al.: "Inhibition of interactions and interconversions of prion protein isoforms by peptide fragments from the C-terminal folded domain"J. Biol. Chem.. 276. 15489-15497 (2001)

Horiuchi, M., 等人：“C 端折叠结构域的肽片段对朊病毒蛋白亚型的相互作用和相互转化的抑制”J.

Ikeda, T., et al.: "Outline of inspection system for bovine spongiform encephalopathy in Japan and future correspondence (in Japanese)"Food Sanitation Research. 52. 33-42 (2001)

Ikeda, T., et al.：“日本牛海绵状脑病检查系统概要和未来对应（日语）”食品卫生研究。

Yamamoto, M. et al.: "Glycidol degrades scrapie mouse prion protein"J.Vet.Med.Sci.. 63. 983-990 (2001)

Yamamoto, M. 等人：“缩水甘油降解痒病小鼠朊病毒蛋白”J.Vet.Med.Sci. 63. 983-990 (2001)

Horiuchi, M.: "Prion diseases in animal (in Japanese)"Uirus. 51. 145-150 (2001)

Horiuchi, M.：“动物朊病毒疾病（日语）”Uirus。

堀内 基広: "動物のプリオン病"ウイルス. 51. 145-150 (2001)

Motohiro Horiuchi：“动物朊病毒病”病毒。 51. 145-150 (2001)