title: Acute cellular uptake of abnormal prion protein is cell type and scrapie-strain independent.
abstract: Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that include Creutzfeldt-Jakob disease, bovine spongiform encephalopathy and sheep scrapie. Although one of the earliest events during TSE infection is the cellular uptake of protease resistant prion protein (PrP-res), this process is poorly understood due to the difficulty of clearly distinguishing input PrP-res from either PrP-res or protease-sensitive PrP (PrP-sen) made by the cell. Using PrP-res tagged with a unique antibody epitope, we examined PrP-res uptake in neuronal and fibroblast cells exposed to three different mouse scrapie strains. PrP-res uptake was rapid and independent of scrapie strain, cell type, or cellular PrP expression, but occurred in only a subset of cells and was influenced by PrP-res preparation and aggregate size. Our results suggest that PrP-res aggregate size, the PrP-res microenvironment, and/or host cell-specific factors can all influence whether or not a cell takes up PrP-res following exposure to TSE infectivity.
authors.affiliation: Rocky Mountain Laboratories, Laboratory of Persistent Viral Diseases, NIAID, NIH, 903 S. 4th Street, Hamilton, Montana 59840, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Greil
authors.forename: Ina M
authors.initials: IM
authors.lastname: Vorberg
authors.forename: Anne E
authors.initials: AE
authors.lastname: Ward
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Meade-White
authors.forename: David A
authors.initials: DA
authors.lastname: Harris
authors.forename: Suzette A
authors.initials: SA
authors.lastname: Priola
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes; D009474:Neurons / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012608:Scrapie / Q000209:etiology / Q000235:genetics / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D011328:Prions; D010447:Peptide Hydrolases