Residues surrounding the glycosylphosphatidylinositol anchor attachment site of PrP modulate prion infection: insight from the resistance of rabbits to prion disease

J Virol. 2010 Jul;84(13):6678-86. doi: 10.1128/JVI.02709-09. Epub 2010 Apr 28.


Prion diseases are a group of transmissible, invariably fatal neurodegenerative diseases that affect both humans and animals. According to the protein-only hypothesis, the infectious agent is a prion (proteinaceous infectious particle) that is composed primarily of PrP(Sc), the disease-associated isoform of the cellular prion protein, PrP. PrP(Sc) arises from the conformational change of the normal, glycosylphosphatidylinositol (GPI)-anchored protein, PrP(C). The mechanism by which this process occurs, however, remains enigmatic. Rabbits are one of a small number of mammalian species reported to be resistant to prion infection. Sequence analysis of rabbit PrP revealed that its C-terminal amino acids differ from those of PrP from other mammals and may affect the anchoring of rabbit PrP through its GPI anchor. Using a cell culture model, this study investigated the effect of the rabbit PrP-specific C-terminal amino acids on the addition of the GPI anchor to PrP(C), PrP(C) localization, and PrP(Sc) formation. The incorporation of rabbit-specific C-terminal PrP residues into mouse PrP did not affect the addition of a GPI anchor or the localization of PrP. However, these residues did inhibit PrP(Sc) formation, suggesting that these rabbit-specific residues interfere with a C-terminal PrP(Sc) interaction site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Glycosylphosphatidylinositols / metabolism*
  • Immunity, Innate*
  • Mice
  • Molecular Sequence Data
  • Pregnancy Proteins / genetics*
  • Pregnancy Proteins / metabolism*
  • Prion Diseases*
  • Protein Binding
  • Rabbits
  • Sequence Alignment


  • Glycosylphosphatidylinositols
  • Plfr protein, mouse
  • Pregnancy Proteins