Prion protein polymorphisms associated with reduced CWD susceptibility limit peripheral PrP^CWD deposition in orally...

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.

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.

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.