Efficient dissemination of prions through preferential transmission to nearby cells.
Despite circumstantial evidence that prions can be found extracellularly or at the surface of infected cells, little is known about how these infectious agents spread from cell to cell. In order to gain better insight into this critical issue, this study used two different cell lines (neuroglial MovS and epithelial Rov cells) that have previously been shown to be permissive for ovine prion multiplication. Co-culture of infected cells and uninfected target cells at a ratio of 1 : 9 resulted in total infection of MovS cells within 10 days but not of Rov cell cultures, suggesting that the efficiency of prion dissemination may vary greatly depending on the type of permissive cell. Analysis of the spatial distribution of the newly infected cells revealed that, although long-range spread could also occur, cells proximal to the infected donor cells consistently accumulated more abnormal PrP, consistent with preferential infection of nearby cells. This experimental approach, focused on dissemination among living cells, could help in the analysis of mechanisms involved in the cell-to-cell spread of prion infections.
Paquet
Sophie
S
Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France.
Langevin
Christelle
C
Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France.
Chapuis
Jérome
J
Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France.
Jackson
Graham S
GS
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Laude
Hubert
H
Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France.
Vilette
Didier
D
Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France.
D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D018621:PrPC Proteins / Q000378:metabolism; D018620:PrPSc Proteins / Q000378:metabolism / Q000472:pathogenicity; D011328:Prions / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits
D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions