Evidence suggesting that PrP is not the infectious agent in Creutzfeldt-Jakob disease.
It has been suggested that the infectious agents of scrapie and Creutzfeldt-Jakob disease (CJD) are 'prions' constituted by a protease resistant glycopeptide, PrP. To analyze the role of PrP in CJD infectivity we re-evaluated the biochemical characteristics of infectivity. First, when the infectious agent is not aggregated, infectivity is exquisitely sensitive to proteinase K treatment, and therefore a proteinase-K-resistant molecule (e.g. PrP) is unlikely to contain information essential for agent replication. Second, removal of sugar residues from Gp34 (the major precursor of the proteolyzed PrP band) failed to reduce infectivity. Third, one-half of the PrP peptides could be separated from significant infectivity using nondenaturing conditions with practical quantitative recovery of infectivity. These studies suggest that PrP in itself is unlikely to be the replicating component of the infectious agent. We suggest that these as yet undefined agents may consist of core protein and nucleic acid that are incompletely assembled in, and protected by, cell membranes. This hypothesis would explain the absence of conventional viral particles in these diseases, account for observed membrane pathology including altered behavior of endogenous membrane proteins, and would be consistent with the replication and transforming properties of CJD that indicate there is an agent specific nucleic acid.
D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002846:Chromatography, Affinity; D007562:Creutzfeldt-Jakob Syndrome / Q000209:etiology*; D006224:Cricetinae; D019286:Endopeptidase K; D010450:Endopeptidases; D006023:Glycoproteins / Q000302:isolation & purification* / Q000378:metabolism
D006023:Glycoproteins; D010450:Endopeptidases; D019286:Endopeptidase K