title: Prion interaction with the 37-kDa/67-kDa laminin receptor on enterocytes as a cellular model for intestinal uptake of prions.
abstract: Enterocytes, a major cell population of the intestinal epithelium, represent one possible barrier to the entry of prions after oral exposure. We established a cell culture system employing enterocytes from different species to study alimentary prion interaction with the 37-kDa/67-kDa laminin receptor LRP/LR. Human, bovine, porcine, ovine, and cervid enterocytes were cocultured with brain homogenates from cervid, sheep, and cattle suffering from chronic wasting disease (CWD), scrapie, and bovine spongiform encephalopathy (BSE), respectively. PrP(CWD), ovine PrP(Sc), and PrP(BSE) all colocalized with LRP/LR on human enterocytes. PrP(CWD) failed to colocalize with LRP/LR on bovine, porcine, and ovine enterocytes. Ovine PrP(Sc) colocalized with the receptor on bovine enterocytes, but failed to colocalize with LRP/LR on cervid and porcine enterocytes. PrP(BSE) failed to colocalize with the receptor on cervid and ovine enterocytes. These data suggest possible oral transmissibility of CWD and sheep scrapie to humans and may confirm the oral transmissibility of BSE to humans, resulting in zoonotic variant Creutzfeldt-Jakob disease. CWD might not be transmissible to cattle, pigs, and sheep. Sheep scrapie might have caused BSE, but may not cause transmissible spongiform encephalopathy in cervids and pigs. BSE may not be transmissible to cervids. Our data recommend the enterocyte model system for further investigations of the intestinal pathophysiology of alimentary prion infections.
authors.affiliation: Laboratorium für Molekulare Biologie, Genzentrum, Institut für Biochemie der LMU, München, Feodor-Lynen-Strasse 25, D-81377 München, Germany.
authors.forename: Dominika
authors.initials: D
authors.lastname: Kolodziejczak
authors.forename: Bianca
authors.initials: B
authors.lastname: Da Costa Dias
authors.forename: Chantal
authors.initials: C
authors.lastname: Zuber
authors.forename: Katarina
authors.initials: K
authors.lastname: Jovanovic
authors.forename: Aadilah
authors.initials: A
authors.lastname: Omar
authors.forename: Julia
authors.initials: J
authors.lastname: Beck
authors.forename: Karen
authors.initials: K
authors.lastname: Vana
authors.forename: Vusi
authors.initials: V
authors.lastname: Mbazima
authors.forename: Juergen
authors.initials: J
authors.lastname: Richt
authors.forename: Bertram
authors.initials: B
authors.lastname: Brenig
authors.forename: Stefan F T
authors.initials: SF
authors.lastname: Weiss
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002417:Cattle; D002460:Cell Line; D003670:Deer; D020895:Enterocytes / Q000378:metabolism*; D006801:Humans; D017096:Prion Diseases / Q000635:transmission; D011328:Prions / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017474:Receptors, Laminin / Q000378:metabolism*; D012756:Sheep; D013552:Swine; D015047:Zoonoses / Q000635:transmission
chemical_list: D011328:Prions; D017474:Receptors, Laminin