This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.01137-07v1 81/19/10786    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Paquet, S. Articles by Vilette, D. Search for Related Content PubMed PubMed Citation Articles by Paquet, S. Articles by Vilette, D.

PrP^c Does Not Mediate Internalization of PrP^Sc but Is Required at an Early Stage for De Novo Prion Infection of Rov Cells

Sophie Paquet, Nathalie Daude, Marie-Pierre Courageot, Jérôme Chapuis, Hubert Laude,^* and Didier Vilette^*

Unité de Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France

Received 24 May 2007/ Accepted 29 June 2007

We have studied the interactions of exogenous prions with an epithelial cell line inducibly expressing PrP^c protein and permissive to infection by a sheep scrapie agent. We demonstrate that abnormal PrP (PrP^Sc) and prion infectivity are efficiently internalized in Rov cells, whether or not PrP^c is expressed. At odds with earlier studies implicating cellular heparan sulfates in PrP^Sc internalization, we failed to find any involvement of such molecules in Rov cells, indicating that prions can enter target cells by several routes. We further show that PrP^Sc taken up in the absence of PrP^c was unable to promote efficient prion multiplication once PrP^c expression was restored in the cells. This observation argues that interaction of PrP^Sc with PrP^c has to occur early, in a specific subcellular compartment(s), and is consistent with the view that the first prion multiplication events may occur at the cell surface.

Published ahead of print on 11 July 2007.

Present address: Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Victoria 3002, Australia.

Present address: University of Alberta, Edmonton ABTG6G2M8, Canada.

Present address: Laboratoire de Biologie Cellulaire et Moléculaire, UFR des Sciences Exactes et Naturelles, Moulin de la Housse, BP 1039 51687 REIMS Cedex 2, France.

This article has been cited by other articles:

• Mahal, S. P., Baker, C. A., Demczyk, C. A., Smith, E. W., Julius, C., Weissmann, C. (2007). Prion strain discrimination in cell culture: The cell panel assay. Proc. Natl. Acad. Sci. USA 104: 20908-20913 [Abstract] [Full Text]