Department of Comparative Biology & Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Calgary Prion Research Unit, University of Calgary, Calgary, AB T2N 4N1, Canada.
Int J Mol Sci. 2021 Feb 25;22(5):2271. doi: 10.3390/ijms22052271.
Chronic wasting disease (CWD) is a prion disease found in both free-ranging and farmed cervids. Susceptibility of these animals to CWD is governed by various exogenous and endogenous factors. Past studies have demonstrated that polymorphisms within the prion protein (PrP) sequence itself affect an animal's susceptibility to CWD. PrP polymorphisms can modulate CWD pathogenesis in two ways: the ability of the endogenous prion protein (PrP) to convert into infectious prions (PrP) or it can give rise to novel prion strains. In vivo studies in susceptible cervids, complemented by studies in transgenic mice expressing the corresponding cervid PrP sequence, show that each polymorphism has distinct effects on both PrP and PrP. It is not entirely clear how these polymorphisms are responsible for these effects, but in vitro studies suggest they play a role in modifying PrP epitopes crucial for PrP to PrP conversion and determining PrP stability. PrP polymorphisms are unique to one or two cervid species and most confer a certain degree of reduced susceptibility to CWD. However, to date, there are no reports of polymorphic cervid PrP alleles providing absolute resistance to CWD. Studies on polymorphisms have focused on those found in CWD-endemic areas, with the hope that understanding the role of an animal's genetics in CWD can help to predict, contain, or prevent transmission of CWD.
慢性消耗病（CWD）是一种在自由放养和养殖鹿科动物中发现的朊病毒病。这些动物对 CWD 的易感性受各种外源性和内源性因素的控制。过去的研究表明，朊蛋白（PrP）序列本身的多态性会影响动物对 CWD 的易感性。PrP 多态性可以通过两种方式调节 CWD 的发病机制：内源性朊蛋白（PrP）转化为感染性朊病毒（PrP）的能力，或者产生新的朊病毒株。易感鹿科动物的体内研究，辅以表达相应鹿科 PrP 序列的转基因小鼠研究，表明每种多态性对 PrP 和 PrP 都有不同的影响。这些多态性如何导致这些影响尚不完全清楚，但体外研究表明，它们在修饰 PrP 表位方面发挥作用，这些表位对于 PrP 向 PrP 的转化和确定 PrP 的稳定性至关重要。PrP 多态性是一种或两种鹿科物种所特有的，大多数会降低对 CWD 的易感性。然而，迄今为止，没有报道表明多态性鹿科 PrP 等位基因对 CWD 具有绝对抗性。对多态性的研究主要集中在 CWD 流行地区发现的多态性上，希望了解动物遗传学在 CWD 中的作用可以帮助预测、控制或预防 CWD 的传播。
