Chronic Wasting Disease of Elk and Deer and Creutzfeldt-Jakob Disease

Abstract

Chronic wasting disease (CWD), a transmissible prion disease that affects elk and deer, poses new challenges to animal and human health. Although the transmission of CWD to humans has not been proven, it remains a possibility. If this were to occur, it is important to know whether the "acquired" human prion disease would show a phenotype including the scrapie prion protein (PrP Sc ) features that differ from those associated with human sporadic prion disease. In this study, we have compared the pathological profiles and PrP Sc characteristics in brains of CWD-affected elk and deer with those in subjects with sporadic Creutzfeldt-Jakob disease (CJD), as well as CJD-affected subjects who might have been exposed to CWD, using histopathology, immunohistochemistry, immunoblotting, conformation stability assay, and N-terminal protein sequencing. Spongiform changes and intense PrP Sc staining were present in several brain regions of CWD-affected animals. Immunoblotting revealed three proteinase K (PK)-resistant bands in CWD, representing different glycoforms of PrP Sc . The unglycosylated PK-resistant PrP Sc of CWD migrated at 21 kDa with an electrophoretic mobility similar to that of type 1 human PrP Sc present in sporadic CJD affecting subjects homozygous for methionine at codon 129 (sCJDMM1). N-terminal sequencing showed that the PK cleavage site of PrP Sc in CWD occurred at residues 82 and 78, similar to that of PrP Sc in sCJDMM1. Conformation stability assay also showed no significant difference between elk CWD PrP Sc and the PrP Sc species associated with sCJDMM1. However, there was a major difference in glycoform ratio of PrP Sc between CWD and sCJDMM1 affecting both subjects potentially exposed to CWD and non-exposed subjects. Moreover, PrPSc of CWD exhibited a distinct constellation of glycoforms distinguishable from that of sCJDMM1 in two-dimensional immunoblots. These findings underline the importance of detailed PrP Sc characterization in trying to detect novel forms of acquired prion disease.

Strain Fidelity of Chronic Wasting Disease upon Murine Adaptation

“…The PK cleavage site was assessed in the third passage of murine CWD and localized to amino acids 73 to 82. This is consistent with the PK-cutting sites for elk CWD at Gly78 and Gly82 (52) and suggests that features of the CWD PrP Sc structure are maintained in the mouse. CWD prions were serially passaged three times.…”

Prion sequence polymorphisms and chronic wasting disease resistance in Illinois white-tailed deer (Odocoileus virginianus)

“…47 In human Creutzfeldt-Jakob disease (CJD), polymorphisms in the amino acid sequence have been associated with alterations in location of these cleavage sites. 48 In addition, polymorphisms quite distal to cleavage sites may alter conformation sufficiently to change proteolytic susceptibility.…”

Prion agent diversity and species barrier

“…It is essential in this respect to document any strain variation of CWD agents, a task that is complicated by the multiplicity of the affected species. The PrP res electropheretic profiles are relatively homogeneous among cervids, both in terms of molecular weights, around 21 kDa for the unglycosylated species, and glycoform ratios [160,209]. However a deeper comparison of the isolates through conformation-dependant immunoassay (CDI, Tab.…”