title: PrP-C1 fragment in cattle brains reveals features of the transmissible spongiform encephalopathy associated PrPsc.
abstract: Three different types of bovine spongiform encephalopathy (BSE) are known and supposedly caused by distinct prion strains: the classical (C-) BSE type that was typically found during the BSE epidemic, and two relatively rare atypical BSE types, termed H-BSE and L-BSE. The three BSE types differ in the molecular phenotype of the disease associated prion protein, namely the N-terminally truncated proteinase K (PK) resistant prion protein fragment (PrPres). In this study, we report and analyze yet another PrPrestype (PrPres-2011), which was found in severely autolytic brain samples of two cows in the framework of disease surveillance in Switzerland in 2011. Analysis of brain tissues from these animals by PK titration and PK inhibitor assays ruled out the process of autolysis as the cause for the aberrant PrPresprofile. Immunochemical characterization of the PrP fragments present in the 2011 cases by epitope mapping indicated that PrPres-2011corresponds in its primary sequence to the physiologically occurring PrP-C1 fragment. However, high speed centrifugation, sucrose gradient assay and NaPTA precipitation revealed biochemical similarities between PrPres-2011and the disease-associated prion protein found in BSE affected cattle in terms of detergent insolubility, PK resistance and PrP aggregation. Although it remains to be established whether PrPres-2011is associated with a transmissible disease, our results point out the need of further research on the role the PrP-C1 aggregation and misfolding in health and disease.
authors.affiliation: NeuroCenter, Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. Electronic address: fabienne.serra@vetsuisse.unibe.ch.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Serra
authors.affiliation: Institute of Parasitology, Vetsuisse Faculty and Medical Faculty, University of Bern, Bern, Switzerland.
authors.forename: Joachim
authors.initials: J
authors.lastname: Müller
authors.affiliation: Canadian Food Inspection Agency, Lethbridge Laboratory, Lethbridge, Alberta, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Gray
authors.affiliation: NeuroCenter, Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Ramona
authors.initials: R
authors.lastname: Lüthi
authors.affiliation: Canadian Food Inspection Agency, Lethbridge Laboratory, Lethbridge, Alberta, Canada.
authors.forename: Sandor
authors.initials: S
authors.lastname: Dudas
authors.affiliation: Canadian Food Inspection Agency, Lethbridge Laboratory, Lethbridge, Alberta, Canada.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Czub
authors.affiliation: NeuroCenter, Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Torsten
authors.initials: T
authors.lastname: Seuberlich
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001329:Autolysis; D015153:Blotting, Western; D001933:Brain Stem / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D003902:Detergents / Q000737:chemistry; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics / Q000378:metabolism*; D018604:Epitope Mapping; D010446:Peptide Fragments / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018620:PrPSc Proteins / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D066329:Protein Aggregates; D012995:Solubility; D013557:Switzerland; D014461:Ultracentrifugation
chemical_list: D003902:Detergents; D010446:Peptide Fragments; D018620:PrPSc Proteins; D066329:Protein Aggregates
keywords: Atypical; BSE; Cattle; Insoluble PrP; Prion protein