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  • The EMBO Journal (2000) 19, 4425 - 4430
  • doi:10.1093/emboj/19.17.4425

Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease

G.J. Raymond1, A. Bossers2, L.D. Raymond1, K.I. O'Rourke3, L.E. McHolland4, P.K. Bryant III4, M.W. Miller5, E.S. Williams6, M. Smits2 and B. Caughey1

  1. NIAID/NIH Rocky Mountain Laboratories, Hamilton, MT 59840, USA
  2. ID-Lelystad, Institute for Animal Science and Health, Lelystad, The Netherlands
  3. USDA/ARS/ADRU, Pullman, WA 99164-7030, USA
  4. USDA/ARS/ABADRL, Laramie, WY 82071, USA
  5. Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, CO 80526-2097, USA
  6. Department of Veterinary Sciences, University of Wyoming, Laramie, WY 82070, USA

Correspondence to:

B. Caughey, E-mail: bcaughey@nih.gov

Received 7 June 2000; Accepted 5 July 2000; Revised 3 July 2000

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of deer and elk, and little is known about its transmissibility to other species. An important factor controlling interspecies TSE susceptibility is prion protein (PrP) homology between the source and recipient species/genotypes. Furthermore, the efficiency with which the protease-resistant PrP (PrP-res) of one species induces the in vitro conversion of the normal PrP (PrP-sen) of another species to the protease-resistant state correlates with the cross-species transmissibility of TSE agents. Here we show that the CWD-associated PrP-res (PrPCWD) of cervids readily induces the conversion of recombinant cervid PrP-sen molecules to the protease-resistant state in accordance with the known transmissibility of CWD between cervids. In contrast, PrPCWD-induced conversions of human and bovine PrP-sen were much less efficient, and conversion of ovine PrP-sen was intermediate. These results demonstrate a barrier at the molecular level that should limit the susceptibility of these non-cervid species to CWD.

  • Keywords:

    • cell-free conversion,
    • chronic wasting disease (CWD),
    • prion protein (PrP),
    • scrapie,
    • transmissible spongiform encephalopathy (TSE)