title: Mouse-adapted sporadic human Creutzfeldt-Jakob disease prions propagate in cell culture.
abstract: Cell based models used for the study of prion diseases have traditionally employed mouse-adapted strains of sheep scrapie prions. To date, attempts to generate human prion propagation in cell culture have been unsuccessful. Rabbit kidney epithelial cells (RK13) are permissive to infection with prions from a variety of species upon expression of cognate PrP transgenes. We explored RK13 cells expressing human PrP for their utility as a cell line capable of sustaining infection with human prions. RK13 cells processed exogenously expressed human PrP similarly to exogenously expressed mouse PrP but were not permissive to infection when exposed to sporadic Creutzfeldt-Jakob disease prions. Transmission of the same sporadic Creutzfeldt Jakob disease prions to wild-type mice generated a strain of mouse-adapted human prions, which efficiently propagated in RK13 cells expressing mouse PrP, demonstrating these cells are permissive to infection by mouse-adapted human prions. Our observations underscore the likelihood that, in contrast to prions derived from non-human mammals, additional unidentified cofactors or subcellular environment are critical for the generation of human prions.
authors.affiliation: Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Lawson
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Vella
authors.forename: James D
authors.initials: JD
authors.lastname: Stewart
authors.forename: Robyn A
authors.initials: RA
authors.lastname: Sharples
authors.forename: Helen
authors.initials: H
authors.lastname: Klemm
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Machalek
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Roberto
authors.initials: R
authors.lastname: Cappai
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Collins
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Hill
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism; D018621:PrPC Proteins / Q000235:genetics* / Q000378:metabolism; D018620:PrPSc Proteins / Q000235:genetics* / Q000378:metabolism; D017096:Prion Diseases / Q000235:genetics* / Q000473:pathology; D011328:Prions / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D012608:Scrapie / Q000235:genetics* / Q000473:pathology / Q000635:transmission
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions