1887

Abstract

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.

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2007-02-01
2024-03-28
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References

  1. Archer F., Bachelin C., Andreoletti O., Besnard N., Perrot G., Langevin C., Le Dur A., Vilette D., Baron-Van Evercooren A. other authors 2004; Cultured peripheral neuroglial cells are highly permissive to sheep prion infection. J Virol 78:482–490 [CrossRef]
    [Google Scholar]
  2. Baron G. S., Wehrly K., Dorward D. W., Chesebro B., Caughey B. 2002; Conversion of raft associated prion protein to the protease-resistant state requires insertion of PrP-res (PrPSc) into contiguous membranes. EMBO J 21:1031–1040 [CrossRef]
    [Google Scholar]
  3. Baron G. S., Magalhães A. C., Prado M. A., Caughey B. 2006; Mouse-adapted scrapie infection of SN56 cells: greater efficiency with microsome-associated versus purified PrP-res. J Virol 80:2106–2117 [CrossRef]
    [Google Scholar]
  4. Beekes M., McBride P. A., Baldauf E. 1998; Cerebral targeting indicates vagal spread of infection in hamsters fed with scrapie. J Gen Virol 79:601–607
    [Google Scholar]
  5. Beringue V., Mallinson G., Kaisar M., Tayebi M., Sattar Z., Jackson G., Anstee D., Collinge J., Hawke S. 2003; Regional heterogeneity of cellular prion protein isoforms in the mouse brain. Brain 126:2065–2073 [CrossRef]
    [Google Scholar]
  6. Brandner S., Isenmann S., Raeber A., Fischer M., Sailer A., Kobayashi Y., Marino S., Weissmann C., Aguzzi A. 1996; Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature 379:339–343 [CrossRef]
    [Google Scholar]
  7. Castilla J., Saá P., Hetz C., Soto C. 2005; In vitro generation of infectious scrapie prions. Cell 121:195–206 [CrossRef]
    [Google Scholar]
  8. Caughey B., Neary K., Buller R., Ernst D., Perry L. L., Chesebro B., Race R. E. 1990; Normal and scrapie-associated forms of prion protein differ in their sensitivities to phospholipase and proteases in intact neuroblastoma cells. J Virol 64:1093–1101
    [Google Scholar]
  9. Christofinis G. J., Beale A. J. 1968; Some biological characters of cell lines derived from normal rabbit kidney. J Pathol Bacteriol 95:377–381 [CrossRef]
    [Google Scholar]
  10. Collinge J. 2001; Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 24:519–550 [CrossRef]
    [Google Scholar]
  11. Cronier S., Laude H., Peyrin J. M. 2004; Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death. Proc Natl Acad Sci U S A 101:12271–12276 [CrossRef]
    [Google Scholar]
  12. Fauré J., Lachenal G., Court M., Hirrlinger J., Chatellard-Causse C., Blot B., Grange J., Schoehn G., Goldberg Y. other authors 2006; Exosomes are released by cultured cortical neurones. Mol Cell Neurosci 31:642–648 [CrossRef]
    [Google Scholar]
  13. Fevrier B., Vilette D., Archer F., Loew D., Faigle W., Vidal M., Laude H., Raposo G. 2004; Cells release prions in association with exosomes. Proc Natl Acad Sci U S A 101:9683–9688 [CrossRef]
    [Google Scholar]
  14. Fields B. N., Knipe D. M. 1990 Virology , 2nd edn. New York: Raven Press;
    [Google Scholar]
  15. Jackson G. S., Hosszu L. L., Power A., Hill A. F., Kenney J., Saibil H., Craven C. J., Waltho J. P., Clarke A. R., Collinge J. 1999; Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations. Science 283:1935–1937 [CrossRef]
    [Google Scholar]
  16. Jeffrey M., Martin S., Gonzalez L., Ryder S. J., Bellworthy S. J., Jackman R. 2001; Differential diagnosis of infections with the bovine spongiform encephalopathy (BSE) and scrapie agents in sheep. J Comp Pathol 125:271–284 [CrossRef]
    [Google Scholar]
  17. Kanu N., Imokawa Y., Drechsel D. N., Williamson R. A., Birkett C. R., Bostock C. J., Brockes J. P. 2002; Transfer of scrapie prion infectivity by cell contact in culture. Curr Biol 12:523–530
    [Google Scholar]
  18. Klohn P. C., Stoltze L., Flechsig E., Enari M., Weissmann C. 2003; A quantitative, highly sensitive cell-based infectivity assay for mouse scrapie prions. Proc Natl Acad Sci U S A 100:11666–11671 [CrossRef]
    [Google Scholar]
  19. Liu T., Li R., Pan T., Liu D., Petersen R. B., Wong B. S., Gambetti P., Sy M. S. 2002; Intercellular transfer of the cellular prion protein. J Biol Chem 277:47671–47678 [CrossRef]
    [Google Scholar]
  20. Medof M. E., Kinoshita T., Nussenzweig V. 1984; Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. J Exp Med 160:1558–1578 [CrossRef]
    [Google Scholar]
  21. Paquet S., Sabuncu E., Delaunay J. L., Laude H., Vilette D. 2004; Prion infection of epithelial Rov cells is a polarized event. J Virol 78:7148–7152 [CrossRef]
    [Google Scholar]
  22. Porto-Carreiro I., Fevrier B., Paquet S., Vilette D., Raposo G. 2005; Prions and exosomes: from PrPc trafficking to PrPsc propagation. Blood Cells Mol Dis 35:143–148 [CrossRef]
    [Google Scholar]
  23. Prusiner S. B. 1998; Prions. Proc Natl Acad Sci U S A 95:13363–13383 [CrossRef]
    [Google Scholar]
  24. Sabuncu E., Petit S., Le Dur A., Lan Lai T., Vilotte J. L., Laude H., Vilette D. 2003; PrP polymorphisms tightly control sheep prion replication in cultured cells. J Virol 77:2696–2700 [CrossRef]
    [Google Scholar]
  25. Schatzl H. M., Laszlo L., Holtzman D. M., Tatzelt J., DeArmond S. J., Weiner R. I., Mobley W. C., Prusiner S. B. 1997; A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis. J Virol 71:8821–8831
    [Google Scholar]
  26. Stahl N., Borchelt D. R., Prusiner S. B. 1990; Differential release of cellular and scrapie prion proteins from cellular membranes by phosphatidylinositol-specific phospholipase C. Biochemistry 29:5405–5412 [CrossRef]
    [Google Scholar]
  27. Taraboulos A., Serban D., Prusiner S. B. 1990; Scrapie prion proteins accumulate in the cytoplasm of persistently infected cultured cells. J Cell Biol 110:2117–2132 [CrossRef]
    [Google Scholar]
  28. Vilette D., Andreoletti O., Archer F., Madelaine M. F., Vilotte J. L., Lehmann S., Laude H. 2001; Ex vivo propagation of infectious sheep scrapie agent in heterologous epithelial cells expressing ovine prion protein. Proc Natl Acad Sci U S A 98:4055–4059 [CrossRef]
    [Google Scholar]
  29. Vilotte J. L., Soulier S., Essalmani R., Stinnakre M. G., Vaiman D., Lepourry L., Da Silva J. C., Besnard N., Dawson M. other authors 2001; Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine PrP. J Virol 75:5977–5984 [CrossRef]
    [Google Scholar]
  30. Vorberg I., Raines A., Story B., Priola S. A. 2004; Susceptibility of common fibroblast cell lines to transmissible spongiform encephalopathy agents. J Infect Dis 189:431–439 [CrossRef]
    [Google Scholar]
  31. Weissmann C. 2004; The state of the prion. Nat Rev Microbiol 2:861–871 [CrossRef]
    [Google Scholar]
  32. Weissmann C., Enari M., Klohn P. C., Rossi D., Flechsig E. 2002; Transmission of prions. J Infect Dis 186 (Suppl. 2):S157–S165 [CrossRef]
    [Google Scholar]
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