Genetic Susceptibility and Biological Characterization of Chronic Wasting Disease

摘要

The goals of this proposal are to: (i) identify prion protein (Prnp) variability in the Wisconsin free-ranging white-tailed deer population, (ii) determine the frequency of these Prnp alleles in CWD-positive and -negative deer, (iii) characterize the effect of these allelic variations on the biochemical and biological properties of the CWD agent and (iv) to determine the likelihood of CWD transmission to humans. Deer Prnp alleles have been sequenced from CWD-positive and -negative deer. Several new alleles have been identified. Two alleles are underrepresented in the CWD-positive animals suggesting they may reduce susceptibility to infection. Tissue from genetically defined, CWD infected deer has been used for determining the protease digestion properties of the wild-type PrPCWD protein and for successfully orally infecting deer with CWD agent of known genotypes. Transgenic mice, expressing cervid PrP, have been successfully infected with CWD agent providing a rodent model for the analysis of CWD infection.