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J. Biol. Chem., Vol. 279, Issue 32, 33847-33854, August 6, 2004
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From the
Robert Koch-Institut,
P26 and ¶P13, Nordufer 20, 13353 Berlin, Germany
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 PrP2730. 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 PrP2730. However, FT-IR spectroscopy revealed that PrP2730 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
-sheet and other secondary structure elements of PrP2730, 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 PrP2730 may provide a versatile tool for molecular strain typing without antibodies and without restrictions to specific TSEs or mammalian species.
Received for publication, April 5, 2004 , and in revised form, May 14, 2004.
* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Both authors contributed equally to this work.
|| To whom correspondence may be addressed: Robert Koch-Institut, P26, Nordufer 20, D-13353 Berlin, Germany. Tel.: 49-30-4547-2396; Fax: 49-30-4547-2267; E-mail: BeekesM{at}rki.de.
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