Prion strain competition and the evolution of new strains

慢性消耗性疾病(CWD)是一种新出现的普恩病毒疾病，影响野生和养殖的鹿群。目前，这种疾病在美国的24个州、加拿大的萨斯喀彻温省和艾伯塔省以及韩国和挪威都存在。由于CWD病原体的“传染性”，这种疾病的地理范围和流行率都在继续扩大。我的研究小组和其他实验室的工作表明，慢性萎缩性脑病并不是以单一的普恩病毒株的形式存在，而是存在多种CWD株。Prion病株在许多重要标准上有所不同，包括病程(潜伏期)、受影响的大脑区域、疾病能够感染的物种(宿主范围)和病原体稳定性。菌株的特异性受一系列因素的控制：特定细胞摄取感染病毒的能力，免疫系统对特定菌株的反应能力，以及感染剂的构象。我们的工作假设是，随着CWD在不同的鹿类物种内和之间传播，独特的CWD菌株已经并将继续出现。这些研究的目标是鉴定病毒株的特性，并阐明在传给新宿主时病毒株选择所涉及的细胞机制。在具体目标#1中，我们将在生物和生化水平上表征我们在CWD物种间传播时所鉴定的新的Pron分离株。然后，这些新的分离株将根据它们的细胞和组织趋向性进行表征

Chronic wasting disease (CWD) is an emerging prion disease affecting wild and farmed cervid populations. The disease is currently present in 24 states in the US, Saskatchewan and Alberta in Canada as well as in South Korea and Norway. Due to the “contagious” nature of the CWD agent, both the geographic range and prevalence of the disease continue to expand. Work from my research group and other laboratories indicate that CWD does not exist as a single “strain” of prion, but rather there are a variety of CWD strains. Prion disease strains differ in a number of important criteria including length of disease (incubation period), region of the brain affected, species the disease is capable of infecting (host range) and disease agent stability. Strain specificity is controlled by a number of factors: ability of specific cells to uptake infectious prions, ability of the immune system to respond to a specific strain and conformation of the infectious agent. Our working hypothesis is that as CWD is transmitted within and between different cervid species, unique CWD strains have and will continue to arise. It is the goal of these studies to characterize prion strains and elucidate the cellular mechanisms involved in strain selection upon passage to a new host. In the Specific Aim #1, we will characterize, at the biological and biochemical levels, novel prion isolates that we have identified upon inter-species transmission of CWD. These novel isolates will then be characterized with respect to their cell and tissue tropisms using