Mouse neuroblastoma cells release prion infectivity associated with exosomal vesicles.
BACKGROUND
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.
Alais
Sandrine
S
LaboRétro INSERM U758, Unité de Virologie Humaine, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France.
Simoes
Sabrina
S
Baas
Dominique
D
Lehmann
Sylvain
S
Raposo
Graça
G
Darlix
Jean Luc
JL
Leblanc
Pascal
P
D000818:Animals; D045744:Cell Line, Tumor; D055354:Exosomes / Q000378:metabolism* / Q000821:virology; D051379:Mice; D009447:Neuroblastoma; D018621:PrPC Proteins / Q000378:metabolism*; D018620:PrPSc Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism* / Q000821:virology; D012608:Scrapie / Q000378:metabolism* / Q000821:virology
D018621:PrPC Proteins; D018620:PrPSc Proteins