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: Christopher S Greil, Ina M Vorberg, Anne E Ward, Kimberly D Meade-White, David A Harris, Suzette A Priola
• Journal: Virology (Virology) Vol. 379 Issue 2 Pg. 284-93 (Sep 30 2008) ISSN: 1096-0341 [Electronic] United States
• PMID: 18692214 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Multiprotein Complexes
• Prions
• Peptide Hydrolases

Topics

• Animals
• Biological Transport, Active
• Brain (metabolism)
• Cell Line
• Cell Membrane (metabolism)
• Kinetics
• Mice
• Mice, Knockout
• Multiprotein Complexes
• Neurons (metabolism)
• Peptide Hydrolases (metabolism)
• Prions (chemistry, genetics, metabolism)
• Protein Binding
• Scrapie (etiology, genetics, metabolism)