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

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Arellano Anaya, Zaïra Esperanza | Savistchenko, Jimmy | Massonneau, Véronique | Lacroux, Caroline, C. | Andréoletti, Olivier | Vilette, Didier

Edité par CCSD ; American Society for Biochemistry and Molecular Biology -

International audience. Prion diseases are characterized by deposits of abnormal conformers of the PrP protein. Although large aggregates of proteinase K-resistant PrP (PrPres) 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 PrPres, 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 PrPres 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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