Natural Resources, School of


Date of this Version



Published in Infection, Genetics and Evolution 84 (2020), 104484.



Copyright © 2020 Elsevier B.V. Used by permission.


Transmissible spongiform encephalopathies can jump species barriers. In relatively few cases is the possible route of transmission thought to be known, mostly involving humans, cattle and sheep. It is thought that sheep might be the cause of Bovine Spongiform Encephalopathy (BSE) and Chronic Wasting Disease (CWD) in cervids, and that humans might have gotten prion disease (e.g., vCJD) from eating meat from BSE+ cows. A looming societal question is whether humans will acquire a prion disease from ingesting prions from CWD+ deer. On an evolutionary tree of the PRNP gene in mammals, deer, sheep and cow are relatively closely related, whereas these three species are relatively distant from humans. If a prion disease jumped the species barrier from cow to humans, the phylogenetic gap from deer to humans is no greater, and sheer evolutionary distance alone cannot explain a CWD species barrier in humans. Aspects of the PRNP gene were compared among these species to search for genetic differences that might influence the permeability of the species barrier. Human prion disease has been associated with having more than four copies of the octarepeat unit (PHGGGWG), whereas deer, sheep and cow all have three copies. Two amino acid positions in the metal-binding region (96 and 97) have been implicated in species barriers (Breydo and Uversky, 2011), whereas no variation was detected in white-tailed deer and mule deer with and without CWD, or in black-tailed deer, Key deer or Coues deer. Four out of 10 differences between deer and human in the β2-α2 loop might preclude CWD prions from converting human PrPC to PrPSc because of disruption of a steric zipper. The reasons for a CWD species barrier between deer and humans, if there is one, is still unresolved.