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Prion strains are differentially released through the exosomal pathway

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Abstract

Cell-to-cell transfer of prions is a crucial step in the spreading of prion infection through infected tissue. At the cellular level, several distinct pathways including direct cell–cell contacts and release of various types of infectious extracellular vesicles have been described that may potentially lead to infection of naïve cells. The relative contribution of these pathways and whether they may vary depending on the prion strain and/or on the infected cell type are not yet known. In this study we used a single cell type (RK13) infected with three different prion strains. We showed that in each case, most of the extracellular prions resulted from active cell secretion through the exosomal pathway. Further, quantitative analysis of secreted infectivity indicated that the proportion of prions eventually secreted was dramatically dependent on the prion strain. Our data also highlight that infectious exosomes secreted from cultured cells might represent a biologically pertinent material for spiking experiments. Also discussed is the appealing possibility that abnormal PrP from different prion strains may differentially interact with the cellular machinery to promote secretion.

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Acknowledgments

We thank Dr. V. Setola for critical reading of the manuscript. This work was partly supported by a grant from ANR-08-MIEN-010 (France) and Z. E. Arellano-Anaya was a recipient of a fellowship from Mexican CONACYT. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Authors and Affiliations

  1. INRA, UMR 1225, IHAP, 31076, Toulouse, France

    Zaira E. Arellano-Anaya, Alvina Huor, Olivier Andréoletti & Didier Vilette

  2. Université de Toulouse, INP, ENVT, UMR 1225, IHAP, 31076, Toulouse, France

    Zaira E. Arellano-Anaya, Alvina Huor, Olivier Andréoletti & Didier Vilette

  3. Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Equipe Différenciation Neuromusculaire, Ecole Normale Supérieure-Lyon, CNRS, UMR 5239, 46 allée d’Italie, 69364, Lyon Cedex 07, France

    Pascal Leblanc

  4. Institut de Médecine Régénératrice et de Biothérapie (I.M.R.B.), Physiopathologie, Diagnostic et Thérapie Cellulaire des Affections Neurodégénératives, Institut National de la Santé et de la Recherche Médicale Université Montpellier 1 U1040 Centre Hospitalo-Universitaire de Montpellier, Université Montpellier 1, Montpellier, France

    Sylvain Lehmann & Monique Provansal

  5. Institut de Génétique Humaine, Centre National de la Recherche Scientifique, UPR 1142, Montpellier, France

    Sylvain Lehmann & Monique Provansal

  6. Institut Curie, UMR 144, CNRS, Structure and Membrane Compartments, Cell and Tissue Imaging Facility (PICT-IBiSA), 26 rue d’Ulm, 75248, Paris Cedex 05, France

    Graça Raposo

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  1. Zaira E. Arellano-Anaya
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Correspondence to Didier Vilette.

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Arellano-Anaya, Z.E., Huor, A., Leblanc, P. et al. Prion strains are differentially released through the exosomal pathway. Cell. Mol. Life Sci. 72, 1185–1196 (2015). https://doi.org/10.1007/s00018-014-1735-8

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  • DOI: https://doi.org/10.1007/s00018-014-1735-8

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