NR AXRI
AU Li,L.; Coulthart,M.B.; Balachandran,A.; Chakrabartty,A.; Cashman,N.R.
TI Quantifying the Species Barrier in Chronic Wasting Disease by a Novel in vitro Conversion Assay
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.47
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that can affect North American cervids (deer, elk, and moose). Although the risk of CWD crossing the species barrier and causing human disease is still unknown, however, definite bovine spongiform encephalopathy (BSE) transmission to humans as variant CJD (vCJD), it would seem prudent to limit the exposure of humans to CWD.
Aim: In view of the fact that BSE can be readily transmitted to non-bovid species, it is important to establish the species susceptibility range of CWD.
Methods: In vitro conversion system was performed by incubation of prions with normal brain homogenates as described before, and protease K (PK) resistant PrP was determined by immunoblotting with 6H4 monoclonal prion antibody.
Results: Our results demonstrate that PrPc from cervids (including moose) can be efficiently converted to a protease-resistant form by incubation with elk CWD prions, presumably due to sequence and structural similarities between these species. Interestingly, hamster shows a high conversion ratio by PrPcWD. Moreover, partial denaturation of substrate PrPc can apparently overcome the structural barriers between more distant species.
Conclusions: Our work correctly predicted the transmission of CWD to a wild moose.
We find a species barrier for prion protein conversion between cervids and other species, however, this barrier might be overcome if the PrPc substrate has been partially denatured in a cellular environment. Such an environment might also promote CWD transmission to non-cervid species, including humans.
Acid/GdnHCl-treated brain PrPc was a superior substrate for the in vitro conversion than PrPc treated at physiological pH. This has implications for the process by which the prion protein is converted in disease.
AD L. Li, N.R. Cashman, University of British Columbia, Brain Research Centre, Canada; M.B. Coulthart, Public Health Agency of Canada, National Microbiology Laboratory, Canada; A. Balachandran, Animal Diseases Research Institute, Canada Food Inspection Agency, National Reference Laboratory for Scrapie and CWD, Canada; A. Chakrabartty, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Canada
SP englisch
PO Schottland