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Letters to Nature

Nature 388, 285-288 (17 July 1997) | ; Received 18 March 1997; Accepted 4 June 1997

Molecular assessment of the potential transmissibilities of BSE and scrapie to humans

Gregory J. Raymond1, James Hope2, David A. Kocisko1,3, Suzette A. Priola1, Lynne D. Raymond1, Alex Bossers4, James Ironside5, Robert G. Will5, Shu G. Chen6, Robert B. Petersen6, Pierluigi Gambetti6, Richard Rubenstein7, Mari A. Smits4, Peter T. Lansbury, Jr3,8 & Byron Caughey1

  1. Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana59840, USA
  2. BBSRC Institute for Animal Health, Compton Laboratory, Compton, Newbury, BerkshireRG20 7NN, UK
  3. Massachusetts Institute of Technology, Department of Chemistry, Cambridge, Massachusetts02139, USA
  4. Department of Bacteriology, DLO-Institute for Animal Science and Health, P.O. Box 65, NL-8200 ABLelystad, The Netherlands
  5. Western General Hospital, CJD Surveillance Unit, EdinburghEH4 2XU, UK
  6. Case Western Reserve University, Institute of Pathology, 2085 Adelbert Road, Cleveland, Ohio44106, USA
  7. NYS Institute for Basic Research, 1050 Forest Hill Road, Staten Island, New York10314, USA
  8. Center for Neurological Diseases, Brigham & Womens Hospital, Harvard Medical School, Boston, Massachusetts02115, USA

Correspondence to: Byron Caughey1 Correspondence and requests for materials should be addressed to J.H. (e-mail: Email: james.hope@bbsrc.ac.uk)

Correspondence to: Correspondence and requests for materials should be addressed to B.C. (e-mail: Email: byron_canghey@nih.gov).

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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.