Prion Strain Competition and the Evolution of New Strains

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Chronic wasting disease (CWD) is an emerging prion disease affecting wild and farmed cervid populations. The disease is currently present in 19 states in the US, Saskatchewan and Alberta in Canada and in South Korea. Due to the "contagious" nature of the CWD agent, the geographic range of the disease continues to expand. Work from my research group and other laboratories indicates 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. Our working hypothesis is that as CWD has been transmitted within and between different cervid species, unique CWD strains have arisen and that this process of strain generation will continue as the disease spreads to new geographic regions. It is the goal of these studies to identify, isolate and characterize CWD strains. CWD isolates from white-tailed deer, mule deer, elk, moose (including polymorphic Prnp variants) from the 3 major geographic foci of endemic CWD (Alberta/Saskatchewan, Colorado/Wyoming, and Wisconsin/Illinois) will be characterized, at the biological level, by determining incubation period/titre as well as occurrence of histopathological lesions and deposition of the infectious form of the prion protein (specific aim #1). The disease-specific conformation of the prion protein (PrPSc) from each isolate will be analyzed biochemically and biophysically to determine whether there are conformational differences between the isolates (specific aim #2). Optical imaging approaches for discriminating between the CWD strains, both in vivo and in vitro, will be developed (specific aim #3). Together, these approaches will allow us to determine the range of CWD strains, predict their spread as well as their potential environmental stability and guide the development of management approaches for these infectious diseases of free-ranging cervids.