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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #330774

Title: Survival time and stability properties of disease-associated prion protein in chronic wasting disease of elk

item MOORE, SARAH - Orise Fellow
item VRENTAS, CATHERINE - Frostburg State University
item WEST GREENLEE, M - Iowa State University
item KONG, Q - Case Western Reserve University (CWRU)
item Greenlee, Justin

Submitted to: American College of Veterinary Pathologists Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 10/6/2016
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Background: The Rocky Mountain elk (Cervus elaphus nelsoni) prion protein gene exhibits amino acid polymorphism at codon 132, with 132L (leucine) and 132M (methionine) allelic variants present in the population. We have previously shown that following experimental oral challenge with chronic wasting disease (CWD) the incubation times of 132LL elk are prolonged, while incubation times for 132LM elk are intermediate, and incubation times for 132MM elk are short. Objective: Investigate potential mechanisms for variations in incubation time in elk of different prion protein genotypes. Methods: The conformational stability of disease-associated prion protein (PrPCWD) from 132MM, 132LM, and 132LL CWD-positive elk from a naturally infected game farm herd was assessed by treatment with increasing concentrations of the denaturant guanidine hydrochloride. Elk brain homogenate was bioassayed in mice expressing the 132MM elk prion protein and the resulting stability of PrPCWD was determined. Results: The stability of PrPCWD from 132MM and 132LM elk were similar to each other and less stable than that from 132LL elk. On first passage and second passage, mice challenged with 132LL elk PrPCWD had prolonged survival times and more stable PrPCWD compared to mice challenged with 132MM PrPCWD. On first passage, survival times and stability profiles for 132LM-challenged mice were similar to 132MM-challenged mice, while on second passage, they were similar to 132LL-challenged mice. Conclusions: In CWD of elk, genotype-associated variations in survival time appear to be associated with differences in conformational stability of PrPCWD in both the natural host and in transgenic mice.