School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, United Kingdom.
J Virol. 2012 Jan;86(1):566-71. doi: 10.1128/JVI.05579-11. Epub 2011 Oct 19.
Preclinical sheep with the highly scrapie-susceptible VRQ/VRQ PRNP genotype secrete prions from the oral cavity. In order to further understand the significance of orally available prions, buccal swabs were taken from sheep with a range of PRNP genotypes and analyzed by serial protein misfolding cyclic amplification (sPMCA). Prions were detected in buccal swabs from scrapie-exposed sheep of genotypes linked to high (VRQ/VRQ and ARQ/VRQ) and low (ARR/VRQ and AHQ/VRQ) lymphoreticular system involvement in scrapie pathogenesis. For both groups, the level of prion detection was significantly higher than that for scrapie-resistant ARR/ARR sheep which were kept in the same farm environment and acted as sentinel controls for prions derived from the environment which might contaminate the oral cavity. In addition, sheep with no exposure to the scrapie agent did not contain any measurable prions within the oral cavity. Furthermore, prions were detected in sheep over a wide age range representing various stages of preclinical disease. These data demonstrate that orally available scrapie prions may be a common feature in sheep incubating scrapie, regardless of the PRNP genotype and any associated high-level accumulation of PrP(Sc) within lymphoreticular tissues. PrP(Sc) was present in buccal swabs from a large proportion of sheep with PRNP genotypes associated with relatively low disease penetrance, indicating that subclinical scrapie infection is likely to be a common occurrence. The significance of positive sPMCA reactions was confirmed by the transmission of infectivity in buccal swab extracts to Tg338 mice, illustrating the likely importance of orally available prions in the horizontal transmission of scrapie.
具有高易感性 VRQ/VRQ PRNP 基因型的临床前绵羊从口腔分泌朊病毒。为了进一步了解可经口获得的朊病毒的意义，从具有一系列 PRNP 基因型的绵羊中采集口腔拭子，并通过连续蛋白错误折叠循环扩增（sPMCA）进行分析。从与淋巴网状系统在朊病毒发病机制中高（VRQ/VRQ 和 ARQ/VRQ）和低（ARR/VRQ 和 AHQ/VRQ）参与相关的暴露于朊病毒的绵羊的口腔拭子中检测到朊病毒。对于这两组，朊病毒检测水平明显高于处于相同农场环境中的对朊病毒具有抗性的 ARR/ARR 绵羊，这些绵羊作为源自可能污染口腔的环境的朊病毒的哨兵对照。此外，未接触过朊病毒制剂的绵羊口腔内未检测到任何可测量的朊病毒。此外，在代表临床前疾病各个阶段的广泛年龄范围内的绵羊中检测到了朊病毒。这些数据表明，可经口获得的传染性海绵状脑病朊病毒可能是在潜伏期感染传染性海绵状脑病的绵羊的共同特征，而与 PRNP 基因型和任何相关的淋巴网状组织中 PrP(Sc)的高水平积累无关。在与相对较低疾病穿透性相关的 PRNP 基因型的绵羊的口腔拭子中存在 PrP(Sc)，表明亚临床传染性海绵状脑病感染可能很常见。通过将感染性传播到 Tg338 小鼠的口腔拭子提取物中，证实了 sPMCA 反应的阳性意义，说明了可经口获得的朊病毒在传染性海绵状脑病的水平传播中的重要性。
