A novel, resistance-linked ovine PrP variant and its equivalent mouse variant modulate the in vitro cell-free conversion of rPrP to PrPres

Louise Kirby, Wilfred Goldmann, Fiona Houston, Andrew C. Gill, Jean C. Manson

Research output: Contribution to journalArticlepeer-review

Abstract

Prion diseases are associated with the conversion of the normal cellular prion protein, PrPC, to the abnormal, disease-associated form, PrPSc. This conversion can be mimicked in vitro by using a cell-free conversion assay. It has recently been shown that this assay can be modified to use bacterial recombinant PrP as substrate and mimic the in vivo transmission characteristics of rodent scrapie. Here, it is demonstrated that the assay replicates the ovine polymorphism barriers of scrapie transmission. In addition, the recently identified ovine PrP variant ARL(168)Q, which is associated with resistance of sheep to experimental BSE, modulates the cell-free conversion of ovine recombinant PrP to PrPres by three different types of PrPSc, reducing conversion efficiencies to levels similar to those of the ovine resistance-associated ARR variant. Also, the equivalent variant in mice (L-164) is resistant to conversion by 87V scrapie. Together, these results suggest a significant role for this position and/or amino acid in conversion.

Original languageEnglish
Pages (from-to)3747-3751
Number of pages5
JournalJournal of General Virology
Volume87
Issue number12
DOIs
Publication statusPublished - Dec 2006

Keywords

  • Amino Acid Substitution
  • Animals
  • Cell-Free System
  • Electrophoresis, Polyacrylamide Gel
  • Immunity, Innate
  • Immunoblotting
  • Mice
  • Polymorphism, Genetic
  • PrPC Proteins
  • PrPSc Proteins
  • Prion Diseases
  • Prions
  • Recombinant Proteins
  • Sheep

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