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

Alicia Otero,Allen Herbst,Rosa Bolea,Chad Johnson,Camilo Duque Velásquez,Judd Aiken,Debbie Mckenzie,Juan José Badiola

doi:10.1186/s12917-019-1794-z

Abstract

BackgroundChronic wasting disease (CWD) is a prion disease affecting members of the Cervidae family. PrPC 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 (PrPCWD) 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 PrPCWD between different PRNP genotypes.ResultsAlthough we detected differences in certain brain areas, globally, the different genotypes showed similar PrPCWD deposition patterns in the brain. However, we found that clinically affected deer expressing H95 PrPC, despite having the longest survival periods, presented less PrPCWD immunoreactivity in particular peripheral organs. In addition, no PrPCWD was detected in skeletal muscle of any of the deer.ConclusionsOur data suggest that expression of H95-PrPC limits peripheral accumulation of PrPCWD as detected by immunohistochemistry. Conversely, infected S96/wt and wt/wt deer presented with similar PrPCWD peripheral distribution at terminal stage of disease, suggesting that the S96-PrPC allele, although delaying CWD progression, does not completely limit the peripheral accumulation of the infectious agent.

Highlights

Chronic wasting disease (CWD) is a prion disease affecting members of the Cervidae family
Abnormal prion protein (PrPCWD) immunolabeling was more intense in the lymph nodes of the head and visceral lymph nodes, whereas lymph nodes of the limbs showed a lower number of positive follicles and milder immunostaining in all deer
We found that the intensity and distribution of PrPCWD deposits in brain and peripheral tissues of prion protein gene (PRNP) polymorphic white-tailed deer was distinct from Q95G95 homozygous deer exposed to the same prion strain (i.e. Wisc-1)

Summary

Introduction

Chronic wasting disease (CWD) is a prion disease affecting members of the Cervidae family. It has been widely documented that certain polymorphisms of the prion protein gene (PRNP), encoding PrPC, play a key role in the susceptibility to prion diseases [11,12,13,14]. The prevalence of CWD is lower in white-tailed deer expressing at least one copy of the H95 or S96 polymorphisms suggesting reduced susceptibility to infection [17]. The direct effect of these polymorphisms on disease progression was evaluated through experimental oral infection studies where CWD source, dose and route of infection were controlled. This experimental infection demonstrated that H95 and S96

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