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Species barriers for chronic wasting disease by in vitro conversion of prion protein

Posted Aug 26 2008 11:29pm
Subject: Species barriers for chronic wasting disease by in vitro conversion
of prion protein
Date: November 3, 2007 at 10:57 am PST

Species barriers for chronic wasting disease by in vitro conversion of prion

Li Li a, Michael B. Coulthart b, Aru Balachandran c, Avi Chakrabartty d,
Neil R. Cashman a,*
a Brain Research Centre, Division of Neurology, Department of Medicine,
University of British Columbia and Vancouver Coastal Health,
UBC Hospital, 2211 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5
b Prion Diseases Program, National Microbiology Laboratory, Public Health
Agency of Canada, Winnipeg, Man., Canada R3E 3R2 Q1
c National Reference Laboratory for Scrapie and CWD, Animal Diseases
Research Institute, Canadian Food Inspection Agency,
3851 Fallowfield Road, Nepean, Ont., Canada K2H 8P9
d University Health Network, Department of Medical Biophysics, University of
Toronto, Toronto, Ont., Canada M5G 1L7
Received 6 October 2007


Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy
that can affect North American cervids (deer, elk, and
moose). Using a novel in vitro conversion system based on incubation of
prions with normal brain homogenates, we now report that
PrPCWD of elk can readily induce the conversion of normal cervid PrP (PrPC)
molecules to a protease-resistant form, but is less efficient
in converting the PrPC of other species, such as human, bovine, hamster, and
mouse. However, when substrate brain homogenates are
partially denatured by acidic conditions (pH 3.5), PrPCWD-induced conversion
can be greatly enhanced in all species. Our results dem-
onstrate 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. Moreover, partial denaturation of substrate PrPC
can apparently overcome the structural barriers between more distant


Although Syrian hamsters were initially deemed resistant to CWD [19], a
recent publication demonstrates that CWD can be transmitted
and adapted to hamster [20].


Substrate denaturation and human health

We confirm with multiple species that acid/GdnHCl-
treated brain PrPC is a superior substrate for in vitro con-
version than untreated PrPC, possibly by overcoming con-
formational barriers in partial denaturation of substrate
PrPC. PrP conversion in scrapie-infected neuroblastoma
cells is believed to occur in endosomes, a low-pH and
reducing environment [26]. The non-ruminant stomach
possesses a low pH lumen, and PrPC is expressed in this
organ [27]. Such acidic (denaturing) organ or cellular
organellar environments might also promote CWD trans-
mission to non-cervid species, including humans.


This work was supported by the Canadian Institutes of
Health Research (Institute of Infection and Immunity, Safe
Food and Water program) and PrioNet Canada.

[20] G.J. Raymond, L.D. Raymond, K.D. Meade-White, A.G. Hughson,
C. Favara, D. Gardner, E.S. Williams, M.W. Miller, R.E. Race, B.
Caughey, Transmission and adaptation of chronic wasting disease to
hamsters and transgenic mice: evidence for strains, J. Virol. 81 (2007)

2007 Elsevier Inc. All rights reserved.

Please cite this article in press as: L. Li et al., Species barriers for
chronic wasting disease by in vitro...,
Biochem. Biophys. Res. Commun. (2007), doi:10.1016/j.bbrc.2007.10.087

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