ABSTRACT

Since the discovery of bovine spongiform encephalopathy (BSE), researchers have orally challenged cattle with infected brain material to study various aspects of disease pathogenesis. Unlike most other pathogens, oral BSE challenge does not always result in the expected clinical presentation and pathology. In a recent study, steers were challenged orally with BSE and all developed clinical signs and were sacrificed and tested. However, despite a similar incubation and clinical presentation, one of the steers did not have detectable PrP^Sc in its brain. Samples from this animal were analysed for genetic differences as well as for the presence of in vitro PrP^Sc seeding activity or infectivity to determine the BSE status of this animal and the potential reasons that it was different. Seeding activity was detected in the brainstem of the abnormal steer but it was approximately one million times less than that found in the normal BSE positive steers. Intra-cranial challenge of bovinized transgenic mice resulted in no transmission of disease. The abnormal steer had different genetic sequences in non-coding regions of the PRNP gene but detection of similar genotypes in Canadian BSE field cases, that showed the expected brain pathology, suggested these differences may not be the primary cause of the abnormal result. Breed composition analysis showed a higher Hereford content in the abnormal steer as well as in two Canadian atypical BSE field cases and several additional abnormal experimental animals. This study could point towards a possible impact of breed composition on BSE pathogenesis.

摘要

自从发现牛海绵状脑病 (BSE) 以来，研究人员已经用受感染的脑材料对牛进行了口服攻击，以研究疾病发病机制的各个方面。与大多数其他病原体不同，口服 BSE 攻击并不总是导致预期的临床表现和病理。在最近的一项研究中，牛用 BSE 进行口服攻击，所有牛都出现了临床症状，并被处死并进行了测试。然而，尽管有类似的孵化和临床表现，其中一只公牛的大脑中没有可检测到的 PrP ^Sc。分析了来自该动物的样本的遗传差异以及体外 PrP ^Sc的存在播种活动或传染性以确定该动物的 BSE 状态及其不同的潜在原因。在异常牛的脑干中检测到播种活动，但比正常 BSE 阳性牛的脑干低约一百万倍。牛化转基因小鼠的颅内攻击未导致疾病传播。异常的阉牛在 PRNP 基因的非编码区具有不同的基因序列，但在加拿大 BSE 现场病例中检测到相似的基因型，显示出预期的脑病理，表明这些差异可能不是导致异常结果的主要原因。品种成分分析表明，异常阉牛以及两个加拿大非典型 BSE 野外案例和其他一些异常实验动物中的赫里福德含量更高。