Discriminating scrapie and bovine spongiform encephalopathy isolates by infrared spectroscopy of pathological prion protein.
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.
Thomzig
Achim
A
Robert Koch-Institut, P26 and P13, Nordufer 20, 13353 Berlin, Germany.
Spassov
Sashko
S
Friedrich
Manuela
M
Naumann
Dieter
D
Beekes
Michael
M
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
D018620:PrPSc Proteins; D018622:PrP 27-30 Protein; D019286:Endopeptidase K