Adams David Bruce
24 Noala Street, Aranda, ACT 2614, Australia.
Open Vet J. 2018;8(3):282-294. doi: 10.4314/ovj.v8i3.7. Epub 2018 Aug 7.
Scrapie in sheep occurs in two forms. Classical scrapie, along with chronic wasting disease in deer, differs from all other prion diseases in being contagious and occurring as propagating epidemics. By contrast, atypical scrapie occurs sporadically and like most other prion diseases, such as Creutzfeldt-Jakob disease in humans, is regarded as non-contagious under natural conditions. This difference motivates the present study, which uses the perspective of evolutionary biology to explore whether atypical or non-contagious scrapie can transform to classical or contagious scrapie when appropriate evolutionary forces are in play. The study begins with an explanation of relevant evolutionary concepts such as evolvability and object of selection and proposes some explicit definitions of key terms such as variation, replication, heritability and strain. Observations of the behaviour of scrapie strains during serial passage in sheep, goats and mice assign the functions of variation, replication and heritability to the scrapie agent and establish it as an object of selection with a capacity for evolvability. Similar observations of strain behaviour in other prion diseases establish prions in general as objects of selection that are able to evolve. Accordingly, it is tenable that non-contagious atypical scrapie can provide progenitors for the prions causing contagious classical scrapie and can be a latent epidemiological threat. A comparison of atypical and classical scrapie identifies an affinity of the scrapie agent for lymphoreticular tissue and predilections for portals of exit and entry as key gain-of-function mutations that endow prion populations in atypical scrapie with the function of communicability or contagiousness. The present study can be seen as the hazard identification step within a process of risk analysis that systematises knowledge in aid of animal health and welfare and biosecurity. It justifies completion of the remaining steps in risk assessment. This task can be assisted by further comparisons of atypical and classical scrapie enlightened by historical records of scrapie disease, the epidemiology of atypical scrapie, the general behaviour of prions and evolutionary biology.
绵羊瘙痒病有两种形式。经典型瘙痒病与鹿的慢性消耗病一样，与所有其他朊病毒疾病不同，具有传染性，并以传播性流行病的形式出现。相比之下，非典型瘙痒病呈散发性，与大多数其他朊病毒疾病（如人类的克雅氏病）一样，在自然条件下被视为无传染性。这种差异促使了本研究，该研究从进化生物学的角度探讨当适当的进化力量起作用时，非典型或无传染性的瘙痒病是否会转变为经典型或传染性瘙痒病。该研究首先解释了诸如可进化性和选择对象等相关进化概念，并对变异、复制、遗传性和毒株等关键术语提出了一些明确的定义。对瘙痒病毒株在绵羊、山羊和小鼠中连续传代过程中的行为观察，赋予了瘙痒病病原体变异、复制和遗传性的功能，并将其确立为具有可进化能力的选择对象。对其他朊病毒疾病中毒株行为的类似观察表明，一般来说朊病毒都是能够进化的选择对象。因此，无传染性的非典型瘙痒病能够为导致传染性经典型瘙痒病的朊病毒提供祖代毒株，并且可能是一种潜在的流行病学威胁，这是合理的。对非典型和经典型瘙痒病的比较表明，瘙痒病病原体对淋巴网状组织的亲和力以及对进出途径的偏好是关键的功能获得性突变，这些突变赋予了非典型瘙痒病中的朊病毒群体传播或传染的功能。本研究可被视为风险分析过程中的危害识别步骤，该过程将知识系统化以促进动物健康、福利和生物安全。它为完成风险评估的其余步骤提供了依据。通过瘙痒病疾病历史记录、非典型瘙痒病流行病学、朊病毒的一般行为和进化生物学对非典型和经典型瘙痒病进行进一步比较，有助于完成这项任务。
