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Updated: Aug 11, 2026

Protein Misfolding Cyclic Amplification of Prions
10:12

Protein Misfolding Cyclic Amplification of Prions

Published on: November 7, 2012

Induced frameshifting mechanism of replication for an information-carrying scrapie prion

P R Wills1

  • 1Department of Physics, University of Auckland, Private Bag, New Zealand.

Microbial Pathogenesis
|April 1, 1989
PubMed

Insights

A novel mistranslation mechanism explains prion protein (PrP) replication and scrapie infectivity. Aberrant PrP variants cause disease by interfering with normal PrP translation and translocation.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Infectious Diseases

Background:

  • Prion diseases, like scrapie, are linked to the infectious prion protein (PrP).
  • The exact mechanism of PrP replication and disease causation remains incompletely understood.
  • Existing models do not fully explain strain variation or discrepancies in PrP sequences.

Purpose of the Study:

  • To describe a specific mistranslation mechanism for prion protein (PrP) replication.
  • To propose a model explaining the aetiology of scrapie and related diseases.
  • To reconcile observed PrP sequences with genetic data.

Main Methods:

  • Analysis of the prion protein (PrP) gene structure, focusing on tandem repeat regions.
  • Modeling of ribosomal frameshifting events during PrP translation.
  • Hypothesizing a feedback mechanism involving aberrant PrP variants.

Main Results:

  • Identified multiple potential ribosomal frameshifting sites within the PrP gene's repeat modules.
  • Proposed that aberrant PrP variants with frameshifted peptides replicate by interfering with normal PrP translation.
  • Demonstrated how this mechanism could explain host-adapted scrapie strains and disease aetiology.

Conclusions:

  • Mistranslated prion protein (PrP) variants are proposed as the infectious agent of scrapie.
  • This model offers a plausible explanation for scrapie strain behavior and disease origins.
  • The hypothesis addresses discrepancies between PrP gene sequences and protein sequences.

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