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

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.