title: PrPc does not mediate internalization of PrPSc but is required at an early stage for de novo prion infection of Rov cells.
abstract: 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.
authors.affiliation: Unité de Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Paquet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Daude
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Courageot
authors.forename: Jérôme
authors.initials: J
authors.lastname: Chapuis
authors.forename: Hubert
authors.initials: H
authors.lastname: Laude
authors.forename: Didier
authors.initials: D
authors.lastname: Vilette
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells; D006497:Heparan Sulfate / Q000378:metabolism; D051379:Mice; D018621:PrPC Proteins / Q000032:analysis / Q000378:metabolism*; D018620:PrPSc Proteins / Q000032:analysis / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism*
chemical_list: D006497:Heparan Sulfate; D018621:PrPC Proteins; D018620:PrPSc Proteins