Department of Forest and Wildlife Ecology, University of Wisconsin, Madison, WI, USA.
Prion. 2012 Apr-Jun;6(2):153-62. doi: 10.4161/pri.19640. Epub 2012 Apr 1.
Chronic wasting disease (CWD) is a major concern for the management of North American cervid populations. This fatal prion disease has led to declines in populations which have high CWD prevalence and areas with both high and low infection rates have experienced economic losses in wildlife recreation and fears of potential spill-over into livestock or humans. Research from human and veterinary medicine has established that the prion protein gene (Prnp) encodes the protein responsible for transmissible spongiform encephalopathies (TSEs). Polymorphisms in the Prnp gene can lead to different prion forms that moderate individual susceptibility to and progression of TSE infection. Prnp genes have been sequenced in a number of cervid species including those currently infected by CWD (elk, mule deer, white-tailed deer, moose) and those for which susceptibility is not yet determined (caribou, fallow deer, sika deer). Over thousands of sequences examined, the Prnp gene is remarkably conserved within the family Cervidae; only 16 amino acid polymorphisms have been reported within the 256 amino acid open reading frame in the third exon of the Prnp gene. Some of these polymorphisms have been associated with lower rates of CWD infection and slower progression of clinical CWD. Here we review the body of research on Prnp genetics of North American cervids. Specifically, we focus on known polymorphisms in the Prnp gene, observed genotypic differences in CWD infection rates and clinical progression, mechanisms for genetic TSE resistance related to both the cervid host and the prion agent and potential for natural selection for CWD-resistance. We also identify gaps in our knowledge that require future research.
慢性消耗病（CWD）是北美鹿科动物种群管理的主要关注点。这种致命的朊病毒病导致了种群数量的下降，而那些 CWD 流行率高的地区和那些高感染率和低感染率的地区都遭受了野生动物娱乐经济损失，并担心朊病毒可能会溢出到牲畜或人类身上。来自人类和兽医医学的研究已经确定，朊病毒蛋白基因（Prnp）编码负责传染性海绵状脑病（TSE）的蛋白。Prnp 基因中的多态性可以导致不同的朊病毒形式，从而调节个体对 TSE 感染的易感性和进展。已经对包括目前感染 CWD 的鹿科动物（麋鹿、骡鹿、白尾鹿、驼鹿）和尚未确定易感性的鹿科动物（驯鹿、赤鹿、梅花鹿）在内的许多鹿科动物的 Prnp 基因进行了测序。在数千个检查的序列中，Prnp 基因在 Cervidae 科内非常保守；仅在 Prnp 基因第三外显子的 256 个氨基酸开放阅读框中报告了 16 个氨基酸多态性。其中一些多态性与较低的 CWD 感染率和较慢的临床 CWD 进展有关。在这里，我们回顾了北美鹿科动物 Prnp 遗传学的研究。具体来说，我们专注于 Prnp 基因中的已知多态性、观察到的 CWD 感染率和临床进展的基因型差异、与鹿宿主和朊病毒剂相关的遗传 TSE 抗性机制以及对 CWD 抗性的自然选择潜力。我们还确定了我们知识中的空白，需要未来的研究。
