Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease

Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of deer and elk, and little is known about its transmissibility to other species. An important factor controlling interspecies TSE susceptibility is prion protein (PrP) homology between the source and recipient species/...

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Bibliographic Details
Published in:The EMBO journal Vol. 19; no. 17; pp. 4425 - 4430
Main Authors: Raymond, G.J., Bossers, A., Raymond, L.D., O'Rourke, K.I., McHolland, L.E., Bryant III, P.K., Miller, M.W., Williams, E.S., Smits, M., Caughey, B.
Format: Journal Article
Language:English
Published: Chichester, UK John Wiley & Sons, Ltd 01-09-2000
Blackwell Publishing Ltd
Oxford University Press
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Cattle
cell-free conversion
chronic wasting disease
chronic wasting disease (CWD)
Cloning, Molecular
deer
DNA Primers
Elk
Genetic Predisposition to Disease
Genotypes
Humans
Molecular Sequence Data
Prion Diseases - genetics
prion protein (PrP)
Prions - chemistry
Prions - genetics
scrapie
Sequence Homology, Amino Acid
Sheep
Species Specificity
transmissible spongiform encephalopathy (TSE)
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Summary:Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of deer and elk, and little is known about its transmissibility to other species. An important factor controlling interspecies TSE susceptibility is prion protein (PrP) homology between the source and recipient species/genotypes. Furthermore, the efficiency with which the protease‐resistant PrP (PrP‐res) of one species induces the in vitro conversion of the normal PrP (PrP‐sen) of another species to the protease‐resistant state correlates with the cross‐species transmissibility of TSE agents. Here we show that the CWD‐associated PrP‐res (PrPCWD) of cervids readily induces the conversion of recombinant cervid PrP‐sen molecules to the protease‐resistant state in accordance with the known transmissibility of CWD between cervids. In contrast, PrPCWD‐induced conversions of human and bovine PrP‐sen were much less efficient, and conversion of ovine PrP‐sen was intermediate. These results demonstrate a barrier at the molecular level that should limit the susceptibility of these non‐cervid species to CWD.
Bibliography:ark:/67375/WNG-PPTV3T19-N
istex:137E3B59F8BEA46B1A705EB474479111FA91AD72
ArticleID:EMBJ7593259
ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ObjectType-Article-1
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Corresponding author e-mail: bcaughey@nih.gov
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.1093/emboj/19.17.4425