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Mouse neuroblastoma cells release prion infectivity associated with exosomal vesicles
Author(s) -
Alais Sandrine,
Simoes Sabrina,
Baas Dominique,
Lehmann Sylvain,
Raposo Graça,
Darlix Jean Luc,
Leblanc Pascal
Publication year - 2008
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1042/bc20080025
Subject(s) - scrapie , infectivity , biology , exosome , microvesicles , virology , cell culture , gene isoform , nucleic acid , microbiology and biotechnology , prion protein , virus , biochemistry , microrna , genetics , gene , disease , medicine , pathology
Background information . TSEs (transmissible spongiform encephalopathies) are neurodegenerative disorders affecting humans and animals. PrP Sc , a conformationally altered isoform of the normal prion protein (PrP C ), 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.