Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies: use of a rapid whole homogenate, protease-free assay

BMC Veterinary Research

Eric M Nicholson³  Stefanie Czub⁴  Maria Caramelli²  Thierry Baron¹  Justin J Greenlee³  Catherine E Vrentas³ 

[1] Agence Nationale de Sécurité Sanitaire (Anses)-Lyon, 31 Avenue Tony Garnier, 69364, Lyon Cedes 07, France;Istituto Zooprofilattico Sperimentale Piemonte Liguria e Valle d'Aost, Via Bologna 148, 10154, Torino, Italy;Virus and Prion Disease Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, 1920 Dayton Road, Ames, IA 50010, USA;National & OIE Reference Laboratories for BSE NCAD/CFIA, Township Road 9-1 (Box 640), Lethbridge/Alberta, Canada

关键词: TSE;    Transmissible spongiform encephalopathy;    Stability;    Scrapie;    PrP;    Prion;    ELISA;    BSE;    Bovine spongiform encephalopathy;   

Others  :  1119471
DOI  :  10.1186/1746-6148-9-167

 received in 2013-04-12, accepted in 2013-08-12,  发布年份 2013

【 摘 要 】

Background

Transmissible Spongiform Encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in cervids, transmissible mink encephalopathy (TME), and bovine spongiform encephalopathy (BSE), are fatal diseases of the nervous system associated with accumulation of misfolded prion protein (PrP^Sc). Different strains of TSEs exist, associated with different PrP^Sc conformations that can be probed by the stability assay, in which PrP^Sc is treated with increasing concentrations of the denaturant guanidine hydrochloride (GdnHCl).

Results

Here, we provide the first comprehensive application of a rapid, protease-free version of the GdnHCl stability assay to brain tissue from cattle experimentally infected with various TSE isolates. Consistent with previous findings from a single Japanese isolate, the L-type isolates of BSE are not distinguishable from classical BSE in this assay. In contrast, H-type isolates of BSE, including our unique isolate of E211K BSE, exhibit higher stability than classical BSE, suggesting that its increased protection against protease digestion at the BSE N-terminus is associated with a higher stability in GdnHCl. While the difference in stability in our version of the assay is likely not large enough for effective use in a diagnostic laboratory setting, the use of alternative experimental conditions may enhance this effect. TSEs from other natural host species that have been passaged in cattle, including CWD and TME, were not distinguishable from classical BSE, while isolates of cattle passaged scrapie exhibited a slight increase in stability as compared to classical BSE.

Conclusions

These results suggest that the core of PrP^Sc, as probed in this assay, has similar stability properties among cattle-passaged TSE isolates and that the conformational differences that lead to changes in the proteinase K cleavage site do not cause large changes in the stability of PrP^Sc from TSE-affected cattle. However, the stability differences observed here will provide a basis of comparison for new isolates of atypical BSE observed in the future and in other geographic locations, especially in the case of H-type BSE.

【 授权许可】

   
2013 Vrentas et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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