Prion protein polymorphisms associated with reduced CWD susceptibility limit peripheral PrP CWD deposition in orally infected white-tailed deer

Abstract

Background: Chronic wasting disease (CWD) is a prion disease affecting members of the Cervidae family. PrP C primary structures play a key role in CWD susceptibility resulting in extended incubation periods and regulating the propagation of CWD strains. We analyzed the distribution of abnormal prion protein (PrP CWD ) aggregates in brain and peripheral organs from orally inoculated white-tailed deer expressing four different PRNP genotypes: Q95G96/Q95G96 (wt/wt), S96/wt, H95/wt and H95/S96 to determine if there are substantial differences in the deposition pattern of PrP CWD between different PRNP genotypes. Results: Although we detected differences in certain brain areas, globally, the different genotypes showed similar PrP CWD deposition patterns in the brain. However, we found that clinically affected deer expressing H95 PrP C , despite having the longest survival periods, presented less PrP CWD immunoreactivity in particular peripheral organs. In addition, no PrP CWD was detected in skeletal muscle of any of the deer. Conclusions: Our data suggest that expression of H95-PrP C limits peripheral accumulation of PrP CWD as detected by immunohistochemistry. Conversely, infected S96/wt and wt/wt deer presented with similar PrP CWD peripheral distribution at terminal stage of disease, suggesting that the S96-PrP C allele, although delaying CWD progression, does not completely limit the peripheral accumulation of the infectious agent.