Purified prion proteins and scrapie infectivity copartition into liposomes.
Considerable evidence indicates that the scrapie prion protein (PrP 27-30) is required for infectivity. Aggregates of PrP 27-30 form insoluble amyloid rods that resist dissociation by nondenaturing detergents. Mixtures of the detergent cholate and phospholipids were found to solubilize purified PrP 27-30 in the form of detergent-lipid-protein complexes. Removal of the cholate by dialysis resulted in the formation of closed liposomes. Both the detergent-lipid-protein complexes and the liposomes often but not always exhibited a 10-fold increase in scrapie infectivity compared to that observed with the rods. No evidence for a prion-associated nucleic acid could be found when the phospholipid vesicles containing PrP 27-30 were digested with nucleases and Zn2+ under conditions that allowed hydrolysis of exogenously added nucleic acids. No filamentous or rod-shaped particles were found amongst prion liposomes by electron microscopy in our search for a putative filamentous "scrapie virus." The partitioning of PrP 27-30 and scrapie infectivity into phospholipid vesicles contends that PrP 27-30 has a central role in scrapie pathogenesis, establishes that the prion amyloid rods are not essential for infectivity, and argues that prions are fundamentally different from viruses.
D000818:Animals; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D008027:Light; D008081:Liposomes; D008854:Microscopy, Electron; D009693:Nucleic Acid Hybridization; D011328:Prions / Q000032:analysis* / Q000472:pathogenicity / Q000648:ultrastructure; D012542:Scattering, Radiation; D014764:Viral Proteins / Q000235:genetics / Q000302:isolation & purification*
D008081:Liposomes; D011328:Prions; D014764:Viral Proteins; D004247:DNA