NR AQQB
AU Vorberg,I.; Raines,A.; Priola,S.A.
TI Acute formation of protease-resistant prion protein does not always lead to persistent scrapie infection in vitro
QU The Journal of Biological Chemistry 2004 Jul 9; 279(28): 29218-25
PT journal article
AB Transmissible spongiform encephalopathies are accompanied by the accumulation of a pathologic isoform of a host-encoded protein, termed prion protein (PrP). Despite the widespread distribution of the cellular isoform of PrP (protease-sensitive PrP; PrP-sen), the disease-associated isoform (protease-resistant PrP; PrPres) appears to be primarily restricted to cells of the nervous and lymphoreticular systems. In order to study why scrapie infection appears to be restricted to certain cells, we followed acute and persistent PrPres formation upon exposure of cells to different scrapie agents. We found that, independent of the cell type and scrapie strain, initial PrPres formation occurred rapidly in cells. However, sustained generation of PrPres and persistent infection did not necessarily follow acute PrPres formation. Persistent PrPres formation and scrapie infection was restricted to one cell line inoculated with the mouse scrapie strain 22L. In contrast to cells that did not become scrapie-infected, the level of PrPres in the 22L-infected cells rapidly increased in the absence of a concomitant increase in the number of PrPres-producing cells. Furthermore, the protein banding pattern of PrPres in these cells changed over time as the cells became chronically infected. Thus, our results suggest that the events leading to the initial formation of PrPres may differ from those required for sustained PrPres formation and infection. This may, at least in part, explain the observation that not all PrP-sen-expressing cells appear to support transmissible spongiform encephalopathy agent replication.
MH Animals; Brain Chemistry; Cell Line; Fibroblasts/cytology/metabolism; Mice; Neuroblastoma/metabolism/pathology; PrPc Proteins/chemistry/*metabolism/pathogenicity; PrPsc Proteins/chemistry/*metabolism/pathogenicity; Prion Diseases/*metabolism; Protein Isoforms/chemistry/*metabolism; Scrapie/*metabolism; Tissue Extracts/chemistry
AD Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840, USA
SP englisch
PO USA