Abstract
THE infectious agents causing scrapie and other transmissible spon-giform encephalopathies have been postulated to consist solely of the protease-resistant form of prion protein (PrPSc)1–6. One unprecedented requirement of the protein-only model is that the 'inheritance9 of pathogen strain differences must be mediated by stable variations in PrPSc structure2,7,8, rather than mutations in an agent-specific nucleic acid9. Strain differences in PrPSc structure have been described for the hyper (HY) and drowsy (DY) strains of hamster transmissible mink encephalopathy (TME)7,8, a scrapie-like disease originating in mink. Although HY and DY PrP are both post-translationally derived from the precursor prion protein (PrPc) they are cleaved at different amino-terminal sites by proteinase K (ref. 8). Here we investigate whether this strain-specific property of PrPSc is transmitted to PrPc during formation of new PrPSc. PrPSc from the HY and DY TME strains converted the protease-sensitive PrPc into two distinct sets of protease-resistant PrP products in a cell-free system. These data provide evidence that self-propagation of PrPSc polymers with distinct three-dimensional structures could be the molecular basis of scrapie strains.
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Bessen, R., Kocisko, D., Raymond, G. et al. Non-genetic propagation of strain-specific properties of scrapie prion protein. Nature 375, 698–700 (1995). https://doi.org/10.1038/375698a0
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DOI: https://doi.org/10.1038/375698a0
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