Papasavva-Stylianou Penelope, Simmons Marion Mathieson, Ortiz-Pelaez Angel, Windl Otto, Spiropoulos John, Georgiadou Soteria
Veterinary Services, Nicosia, Cyprus.
Animal and Plant Health Agency, New Haw, Addlestone, Surrey, United Kingdom.
J Virol. 2017 Oct 27;91(22). doi: 10.1128/JVI.01142-17. Print 2017 Nov 15.
This report presents the results of experimental challenges of goats with scrapie by both the intracerebral (i.c.) and oral routes, exploring the effects of polymorphisms at codon 146 of the goat gene on resistance to disease. The results of these studies illustrate that while goats of all genotypes can be infected by i.c. challenge, the survival distribution of the animals homozygous for asparagine at codon 146 was significantly shorter than those of animals of all other genotypes (chi-square value, 10.8; = 0.001). In contrast, only those animals homozygous for asparagine at codon 146 (NN animals) succumbed to oral challenge. The results also indicate that any cases of infection in non-NN animals can be detected by the current confirmatory test (immunohistochemistry), although successful detection with the rapid enzyme-linked immunosorbent assay (ELISA) was more variable and dependent on the polymorphism. Together with data from previous studies of goats exposed to infection in the field, these data support the previously reported observations that polymorphisms at this codon have a profound effect on susceptibility to disease. It is concluded that only animals homozygous for asparagine at codon 146 succumb to scrapie under natural conditions. In goats, like in sheep, there are PRNP polymorphisms that are associated with susceptibility or resistance to scrapie. However, in contrast to the polymorphisms in sheep, they are more numerous in goats and may be restricted to certain breeds or geographical regions. Therefore, eradication programs must be specifically designed depending on the identification of suitable polymorphisms. An initial analysis of surveillance data suggested that such a polymorphism in Cypriot goats may lie in codon 146. In this study, we demonstrate experimentally that NN animals are highly susceptible after i.c. inoculation. The presence of a D or S residue prolonged incubation periods significantly, and prions were detected in peripheral tissues only in NN animals. In oral challenges, prions were detected only in NN animals, and the presence of a D or S residue at this position conferred resistance to the disease. This study provides an experimental transmission model for assessing the genetic susceptibility of goats to scrapie.
本报告介绍了通过脑内（i.c.）和口服途径用羊瘙痒病对山羊进行实验性攻毒的结果，探讨了山羊基因第146密码子多态性对疾病抗性的影响。这些研究结果表明，虽然所有基因型的山羊都可通过脑内攻毒感染，但第146密码子为天冬酰胺纯合子的动物的存活分布显著短于所有其他基因型的动物（卡方值，10.8；P = 0.001）。相比之下，只有那些第146密码子为天冬酰胺纯合子的动物（NN动物）在口服攻毒后死亡。结果还表明，目前的确诊试验（免疫组织化学）可检测到非NN动物的任何感染病例，尽管快速酶联免疫吸附测定（ELISA）的成功检测更具变异性且取决于多态性。结合先前对野外暴露于感染的山羊的研究数据，这些数据支持先前报道的观察结果，即该密码子的多态性对疾病易感性有深远影响。得出的结论是，只有第146密码子为天冬酰胺纯合子的动物在自然条件下会死于羊瘙痒病。在山羊中，与绵羊一样，存在与羊瘙痒病易感性或抗性相关的PRNP多态性。然而，与绵羊中的多态性不同，它们在山羊中更多，并且可能限于某些品种或地理区域。因此，必须根据合适多态性的鉴定专门设计根除计划。对监测数据的初步分析表明，塞浦路斯山羊中的这种多态性可能位于第146密码子。在本研究中，我们通过实验证明NN动物在脑内接种后高度易感。D或S残基的存在显著延长了潜伏期，并且仅在NN动物的外周组织中检测到朊病毒。在口服攻毒中，仅在NN动物中检测到朊病毒，并且该位置D或S残基的存在赋予了对疾病的抗性。本研究提供了一个用于评估山羊对羊瘙痒病遗传易感性的实验性传播模型。
