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 (PrP Sc) 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 PrP Sc taken up in the absence of PrPc was unable to promote efficient prion multiplication once PrPc expression was restored in the cells. This..