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 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 in vitro, ex vivo and in vivo assays (specific aim #2). To elucidate the properties of a prion agent that dictate strain, we will use a variety of physiochemical approaches to modify the prion strain (specific aim #3). Together these approaches will allow us to determine the range of CWD strains, predict their spread as well as their stability and provide mechanism for changing strain tropisms.**************************************************