Novel Proteinaceous Infectious Particles Cause Scrapie

TLDR

Scrapie is a degenerative CNS disease in sheep and goats that appears after a prolonged incubation period, and understanding its agent may shed light on other neurodegenerative disorders. The study aims to introduce the term “prion” for a small proteinaceous infectious particle that resists most nucleic‑acid–targeting inactivation procedures. The authors demonstrated the agent’s protein nature by showing protease sensitivity, resistance to alkali, lack of inactivation by nucleic‑acid–specific treatments, and size heterogeneity with a minimal form around 50 kDa. Six lines of evidence—including protease sensitivity, alkali resistance, failure of nucleic‑acid–specific inactivation, and size heterogeneity—confirm that the scrapie agent is a protein required for infectivity.

Abstract

After infection and a prolonged incubation period, the scrapie agent causes a degenerative disease of the central nervous system in sheep and goats. Six lines of evidence including sensitivity to proteases demonstrate that this agent contains a protein that is required for infectivity. Although the scrapie agent is irreversibly inactivated by alkali, five procedures with more specificity for modifying nucleic acids failed to cause inactivation. The agent shows heterogeneity with respect to size, apparently a result of its hydrophobicity; the smallest form may have a molecular weight of 50,000 or less. Because the novel properties of the scrapie agent distinguish it from viruses, plasmids, and viroids, a new term "prion" is proposed to denote a small pro teinaceous in fectious particle which is resistant to inactivation by most procedures that modify nucleic acids. Knowledge of the scrapie agent structure may have significance for understanding the causes of several degenerative diseases.