title: Discriminating scrapie and bovine spongiform encephalopathy isolates by infrared spectroscopy of pathological prion protein.
abstract: For the surveillance of transmissible spongiform encephalopathies (TSEs) in animals and humans, the discrimination of different TSE strains causing scrapie, BSE, or Creutzfeldt-Jakob disease constitutes a substantial challenge. We addressed this problem by Fourier transform-infrared (FT-IR) spectroscopy of pathological prion protein PrP27-30. Different isolates of hamster-adapted scrapie (263K, 22A-H, and ME7-H) and BSE (BSE-H) were passaged in Syrian hamsters. Two of these agents, 22A-H and ME7-H, caused TSEs with indistinguishable clinical symptoms, neuropathological changes, and electrophoretic mobilities and glycosylation patterns of PrP27-30. However, FT-IR spectroscopy revealed that PrP27-30 of all four isolates featured different characteristics in the secondary structure, allowing a clear distinction between the passaged TSE agents. FT-IR analysis showed that phenotypic information is mirrored in beta-sheet and other secondary structure elements of PrP27-30, also in cases where immunobiochemical typing failed to detect structural differences. If the findings of this study hold true for nonexperimental TSEs in animals and humans, FT-IR characterization of PrP27-30 may provide a versatile tool for molecular strain typing without antibodies and without restrictions to specific TSEs or mammalian species.
authors.affiliation: Robert Koch-Institut, P26 and P13, Nordufer 20, 13353 Berlin, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Thomzig
authors.forename: Sashko
authors.initials: S
authors.lastname: Spassov
authors.forename: Manuela
authors.initials: M
authors.lastname: Friedrich
authors.forename: Dieter
authors.initials: D
authors.lastname: Naumann
authors.forename: Michael
authors.initials: M
authors.lastname: Beekes
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D006224:Cricetinae; D004195:Disease Models, Animal; D016643:Encephalopathy, Bovine Spongiform / Q000503:physiopathology; D019286:Endopeptidase K / Q000378:metabolism; D008647:Mesocricetus; D018622:PrP 27-30 Protein / Q000737:chemistry*; D018620:PrPSc Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D012608:Scrapie / Q000503:physiopathology; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution
chemical_list: D018620:PrPSc Proteins; D018622:PrP 27-30 Protein; D019286:Endopeptidase K