Mouse neuroblastoma cells release prion infectivity associated with exosomal vesicles

Biology of the Cell - Tập 100 Số 10 - Trang 603-618 - 2008
Sandrine Alais1,2, Sabrina Simoes3, Dominique Baas4,2, Sylvain Lehmann5, Graça Raposo3, Jean Luc Darlix1,2, Pascal Leblanc1,2
1LaboRétro INSERM U758, Unité de Virologie Humaine, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France
2Université Lyon 1, IFR 128 Biosciences Lyon-Gerland, Lyon-Biopôle, Lyon, France
3Institut Curie, CNRS-UMR144 Structure et Compartiments Membranaires, 26 rue d'Ulm, 75248 Paris cedex 05, France
4LBMC, UMR5161 CNRS-UCBL, Ecole Normale Supérieure de Lyon 69364 Lyon cedex 07, France
5Institut de Génétique Humaine (IGH), CNRS, UPR 1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France

Tóm tắt

Background information. TSEs (transmissible spongiform encephalopathies) are neurodegenerative disorders affecting humans and animals. PrPSc, a conformationally altered isoform of the normal prion protein (PrPC), is thought to be the pathogenic agent. However, the biochemical composition of the prion agent is still matter of debate. The potential transmission risk of the prion agent through biological fluids has been shown, but the development of competitive diagnostic tests and treatment for TSEs requires a more comprehensive knowledge of the agent and the cellular mechanisms by which it is disseminated. With this aim, we initiated characterization of the prion agent and the pathways by which it can be propagated using the cellular model system neuroblastoma (N2a).Results. The present study shows that N2a cells infected with scrapie release the prion agent into the cell culture medium in association with exosome‐like structures and viral particles of endogenous origin. We found that both prion proteins and scrapie infectivity are mainly associated with exosome‐like structures that contain viral envelope glycoprotein and nucleic acids, such as RNAs.Conclusions. The dissemination of prions in N2a cell culture is mediated through the exosomal pathway.

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Biology of the Cell

Tập 100 Số 10

603-618

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