Species barriers for chronic wasting disease by in vitro conversion of prion protein.
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 PrP(CWD) of elk can readily induce the conversion of normal cervid PrP (PrP(C)) molecules to a protease-resistant form, but is less efficient in converting the PrP(C) of other species, such as human, bovine, hamster, and mouse. However, when substrate brain homogenates are partially denatured by acidic conditions (pH 3.5), PrP(CWD)-induced conversion can be greatly enhanced in all species. Our results demonstrate that PrP(C) 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 PrP(C) can apparently overcome the structural barriers between more distant species.
Li
Li
L
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.
Coulthart
Michael B
MB
Balachandran
Aru
A
Chakrabartty
Avi
A
Cashman
Neil R
NR
D000595:Amino Acid Sequence; D000818:Animals; D003670:Deer; D006801:Humans; D008969:Molecular Sequence Data; D018621:PrPC Proteins / Q000737:chemistry* / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D034081:Wasting Disease, Chronic / Q000235:genetics* / Q000378:metabolism*
D018621:PrPC Proteins