Abstract
More than a million cattle infected with bovine spongiform encephalopathy (BSE) may have entered the human food chain1. Fears that BSE might transmit to man were raised when atypical cases of Creutzfeldt–Jakob disease (CJD), a human transmissible spongiform encephalopathy (TSE), emerged in the UK2,3. In BSE and other TSE diseases, the conversion of the protease-sensitive host prion protein (PrP-sen) to a protease-resistant isoform (PrP-res) is an important event in pathogenesis4,5,6,7. Biological aspects of TSE diseases are reflected in the specificities of in vitro PrP conversion reactions8,9,10,11,12. Here we show that there is a correlation between in vitro conversion efficiencies and known transmissibilities of BSE, sheep scrapie and CJD. On this basis, we used an in vitro system to gauge the potential transmissibility of scrapie and BSE to humans. We found limited conversion of human PrP-sen to PrP-res driven by PrP-res associated with both scrapie (PrPSc) and BSE (PrPBSE). The efficiencies of these heterologous conversion reactions were similar but much lower than those of relevant homologous conversions. Thus the inherent ability of these infectious agents of BSE and scrapie to affect humans following equivalent exposure may be finite but similarly low.
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Acknowledgements
We thank B. Chesebro, C. Bostock and our colleagues at the Rocky Mountain Laboratories and the Institute for Animal Heath for their suggestions and critiques of this manuscript and our experimental design, and A. Chong for technical assistance, Part of this work was funded by the UK Ministry of Agriculture, Fisheries and Food (J.H.) and by NIH grants and Britton Fund to P.G.
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Raymond, G., Hope, J., Kocisko, D. et al. Molecular assessment of the potential transmissibilities of BSE and scrapie to humans. Nature 388, 285–288 (1997). https://doi.org/10.1038/40876
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DOI: https://doi.org/10.1038/40876
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