title: Canine MDCK cell lines are refractory to infection with human and mouse prions.
abstract: Influenza vaccine production in embryonated eggs is associated with many disadvantages, and production in cell culture systems is a viable alternative. Madin Darby canine kidney (MDCK) cells are permissive for a variety of orthomyxoviruses and have proven particularly suitable for vaccine mass production. However, mammalian cells harboring the Prnp gene can theoretically acquire prion infections. Here, we have attempted to infect MDCK cells and substrains thereof with prions. We found that MDCK cells did not produce any protease-resistant PrP(Sc) upon exposure to brain homogenates derived from humans suffering from Creutzfeldt-Jakob disease (CJD) or from mice infected with Rocky Mountain Laboratory (RML) scrapie prions. Further, transmission of MDCK lysates to N2aPK1 cells did not induce formation of PrP(Sc) in the latter. PrP(C) biogenesis and processing in MDCK cells were similar to those of prion-sensitive N2aPK1 cells. However, steady-state levels of PrP(C) were very low, and PrP(C) did not partition with detergent-resistant membranes upon density gradient analysis. These factors may account for their resistance to infection. Alternatively, prion resistance may be related to the specific sequence of canine Prnp, as suggested by the lack of documented prion diseases in dogs.
authors.affiliation: Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstrasse 12, Zürich, Switzerland. magdalini.polymenidou@usz.ch
authors.forename: Magdalini
authors.initials: M
authors.lastname: Polymenidou
authors.forename: Heidi
authors.initials: H
authors.lastname: Trusheim
authors.forename: Lena
authors.initials: L
authors.lastname: Stallmach
authors.forename: Rita
authors.initials: R
authors.lastname: Moos
authors.forename: Christian
authors.initials: C
authors.lastname: Julius
authors.forename: Gino
authors.initials: G
authors.lastname: Miele
authors.forename: Claudia
authors.initials: C
authors.lastname: Lenz-Bauer
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D007562:Creutzfeldt-Jakob Syndrome; D004285:Dogs; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018621:PrPC Proteins / Q000737:chemistry; D018620:PrPSc Proteins / Q000737:chemistry; D011328:Prions / Q000472:pathogenicity*; D012608:Scrapie; D016415:Sequence Alignment
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions