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Journal of Virology, October 2007, p. 10786-10791, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.01137-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

PrPc Does Not Mediate Internalization of PrPSc but Is Required at an Early Stage for De Novo Prion Infection of Rov Cells{triangledown}

Sophie Paquet,{dagger} Nathalie Daude,{ddagger} 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 PrPc protein and permissive to infection by a sheep scrapie agent. We demonstrate that abnormal PrP (PrPSc) and prion infectivity are efficiently internalized in Rov cells, whether or not PrPc is expressed. At odds with earlier studies implicating cellular heparan sulfates in PrPSc 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 PrPSc taken up in the absence of PrPc was unable to promote efficient prion multiplication once PrPc expression was restored in the cells. This observation argues that interaction of PrPSc with PrPc 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.


* Corresponding author. Mailing address for D. Vilette: UMR 1225, INRA/ENVT, 23 Chemin des Capelles, 31076 Toulouse, France. Phone: 33561193997. Fax: 33561193834. E-mail: d.vilette{at}envt.fr. Mailing address for H. Laude: Unité Virologie Immunologie Moléculaires, INRA, 78350 Jouy-en-Josas, France. Phone: 33134652600. Fax: 33134652621. E-mail: hubert.laude{at}jouy.inra.fr

{triangledown} Published ahead of print on 11 July 2007.

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

{ddagger} 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.


Journal of Virology, October 2007, p. 10786-10791, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.01137-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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