Non-genetic propagation of strain-specific properties of scrapie prion protein (original) (raw)

Nature volume 375, pages 698–700 (1995)Cite this article

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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Authors and Affiliations

  1. Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, 59840, USA
    Richard A. Bessen, David A. Kocisko, Gregory J. Raymond & Byron Caughey
  2. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA
    David A. Kocisko, Santosh Nandan & Peter T. Lansbury

Authors

  1. Richard A. Bessen
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  2. David A. Kocisko
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  3. Gregory J. Raymond
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  4. Santosh Nandan
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  5. Peter T. Lansbury
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  6. Byron Caughey
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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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