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Publication : Recovery of small infectious PrP(res) aggregates from prion-infected cultured cells.

First Author  Anaya ZE Year  2011
Journal  J Biol Chem Volume  286
Issue  10 Pages  8141-8
PubMed ID  21212268 Mgi Jnum  J:170530
Mgi Id  MGI:4946844 Doi  10.1074/jbc.M110.165233
Citation  Anaya ZE, et al. (2011) Recovery of small infectious PrP(res) aggregates from prion-infected cultured cells. J Biol Chem 286(10):8141-8
abstractText  Prion diseases are characterized by deposits of abnormal conformers of the PrP protein. Although large aggregates of proteinase K-resistant PrP (PrP(res)) are infectious, the precise relationships between aggregation state and infectivity remain to be established. In this study, we have fractionated detergent lysates from prion-infected cultured cells by differential ultracentrifugation and ultrafiltration and have characterized a previously unnoticed PrP species. This abnormal form is resistant to proteinase K digestion but, in contrast to typical aggregated PrP(res), remains in the soluble fraction at intermediate centrifugal forces and is not retained by filters of 300-kDa cutoff. Cell-based assay and inoculation to animals demonstrate that these entities are infectious. The finding that cell-derived small infectious PrP(res) aggregates can be recovered in the absence of strong in vitro denaturating treatments now gives a biological basis for investigating the role of small PrP aggregates in the pathogenicity and/or the multiplication cycle of prions.
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