Non-genetic Propagation of Strain-Specific Properties of Scrapie Prion Protein

Nature. 1995 Jun 22;375(6533):698-700. doi: 10.1038/375698a0.

Abstract

The infectious agents causing scrapie and other transmissible spongiform encephalopathies have been postulated to consist solely of the protease-resistant form of prion protein (PrPSc). One unprecedented requirement of the protein-only model is that the 'inheritance' of pathogen strain differences must be mediated by stable variations in PrPSc structure, rather than mutations in an agent-specific nucleic acid. Strain differences in PrPSc structure have been described for the hyper (HY) and drowsy (DY) strains of hamster transmissible mink encephalopathy (TME), a scrapie-like disease originating in mink. Although HY and DY PrPSc 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.

MeSH terms

  • Animals
  • Cetylpyridinium / pharmacology
  • Cricetinae
  • Culture Techniques
  • Endopeptidase K
  • Guanidine
  • Guanidines / pharmacology
  • Mesocricetus
  • PrPC Proteins / chemistry
  • PrPC Proteins / metabolism*
  • PrPSc Proteins / chemistry
  • PrPSc Proteins / metabolism*
  • Prion Diseases / metabolism
  • Prions / classification
  • Prions / metabolism*
  • Serine Endopeptidases / metabolism
  • Species Specificity

Substances

  • Guanidines
  • PrPC Proteins
  • PrPSc Proteins
  • Prions
  • Cetylpyridinium
  • Serine Endopeptidases
  • Endopeptidase K
  • Guanidine