Molecular basis of scrapie strain glycoform variation.
Transmissible spongiform encephalopathies (TSE) are characterized by the conversion of a protease-sensitive host glycoprotein, prion protein or PrP-sen, to a protease-resistant form (PrP-res). PrP-res molecules that accumulate in the brain and lymphoreticular system of the host consist of three differentially glycosylated forms. Analysis of the relative amounts of the PrP-res glycoforms has been used to discriminate TSE strains and has become increasingly important in the differential diagnosis of human TSEs. However, the molecular basis of PrP-res glycoform variation between different TSE agents is unknown. Here we report that PrP-res itself can dictate strain-specific PrP-res glycoforms. The final PrP-res glycoform pattern, however, can be influenced by the cell and significantly altered by subtle changes in the glycosylation state of PrP-sen. Thus, strain-specific PrP-res glycosylation profiles are likely the consequence of a complex interaction between PrP-res, PrP-sen, and the cell and may indicate the cellular compartment in which the strain-specific formation of PrP-res occurs.
Laboratory of Persistent Viral Diseases, NIAID, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA.
Ina
I
Vorberg
Suzette A
SA
Priola
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002474:Cell-Free System; D006031:Glycosylation; D006801:Humans; D051379:Mice; D010641:Phenotype; D018620:PrPSc Proteins / Q000737:chemistry* / Q000378:metabolism; D017096:Prion Diseases / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018620:PrPSc Proteins