Rapid Detection of CWD PrP: Comparison of Tests Designed for the Detection of BSE or Scrapie

Institute for Zoo and Wildlife Research (IZW), Alfred-Kowalke-Str., Berlin, Germany.
Transboundary and Emerging Diseases (Impact Factor: 2.94). 12/2011; 59(5):405-15. DOI: 10.1111/j.1865-1682.2011.01294.x
Source: PubMed


Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) mainly affecting cervids in North America. The accumulation of an abnormal form of host-encoded prion protein (PrP(CWD) ) in the CNS and lymphoid tissues is characteristic of the disease and known to be caused by pathogenic prion proteins (PrP(res) ), which are thought to be transmitted mainly by contact with body fluids, such like saliva. Species known to be naturally infected by CWD include Rocky Mountain elk (Cervus elaphus nelsoni), white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus). Recently, large-scale disease eradication or control programs have been attempted to curtail the spread of disease. But reports of diseased free-ranging and farmed cervids in many locations in the USA and Canada are still continuing. The goal of this study was to find sensitive rapid test systems that are reliably able to detect CWD-associated PrP(CWD) in cervids, thereby reviewing an important control tool in case the disease spreads further and reaches Europe. Seven tests, originally developed for the detection of other TSE diseases such as Scrapie and bovine spongiform encephalopathy, including two Western blots, four enzyme-linked immunosorbent assays (ELISAs), and one lateral flow device, were included in this study. All seven tests evaluated were able to detect pathogenic prion proteins (PrP(CWD) ) in Northern American infected animals and distinguish physiologic prion protein (PrP(c) ) in brainstem (obex region) and lymph node samples from North American and European cervids, respectively. However, the specificity and sensitivity of the tests differed significantly. Highly sensitive tests for the detection of prion proteins are an important tool both for the design of effective disease surveillance and control strategies and the safety of the food chain. Thus, this study contributes to the emergency preparedness against CWD.

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    • "The result of these efforts has been the virtual elimination of BSE in Europe. PK-dependent immunoassays have also been used to identify scrapie and CWD infected ovine and cervid flocks and herds, respectively (Blasche et al., 2012). These tests have been used to substantially reduce the prevalence of prion disease in agriculturally important animals. "
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    ABSTRACT: Infectious proteins (prions) are, ironically, defined by their resistance to proteolytic digestion. A defining characteristic of the transmissible isoform of the prion protein (PrP(Sc)) is its partial resistance to proteinase K (PK) digestion. Diagnosis of prion disease typically relies upon immunodetection of PK-digested PrP(Sc) by Western blot, ELISA or immunohistochemical detection. PK digestion has also been used to detect differences in prion strains. Thus, PK has been a crucial tool to detect and, thereby, control the spread of prions. PK has also been used as a tool to probe the structure of PrP(Sc). Mass spectrometry and antibodies have been used to identify PK cleavage sites in PrP(Sc). These results have been used to identify the more accessible, flexible stretches connecting the β-strand components in PrP(Sc). These data, combined with physical constraints imposed by spectroscopic results, were used to propose a qualitative model for the structure of PrP(Sc). Assuming that PrP(Sc) is a four rung β-solenoid, we have threaded the PrP sequence to satisfy the PK proteolysis data and other experimental constraints. Copyright © 2015. Published by Elsevier B.V.
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