The Generative Brain

Pritzkow S et al. 2022, North American and Norwegian chronic wasting disease prions exhibit different potential for interspecies transmission and zoonotic risk (J Infect Dis 225:542)

This is an in vitro strain comparison of chronic wasting disease (CWD) prions from six cervid isolates, three North American (whitetail deer, elk, mule deer) and three Norwegian (moose, reindeer, red deer), run by protein misfolding cyclic amplification (PMCA) against prion protein substrates from several mammals. Two numbers come out of it: a spillover score, summing conversion across non-human substrates after one round, and a zoonotic score, summing conversion of human prion protein with methionine and valine at codon 129 after a second round. The Norwegian reindeer isolate had the highest spillover score of all six (12, against 9 for whitetail deer and moose, 8 for red deer, 6 for mule deer and 3 for elk), yet all three Norwegian isolates scored zero for human conversion while all three North American isolates converted human prion protein in round two, whitetail deer highest. The authors read the two groups as different strains with different spillover and zoonotic potential, and say the result must be taken cautiously because PMCA is a test tube reaction, not an infection. The work sits beside the humanized mouse study that found no transmission of Norwegian reindeer and moose CWD, and both point the same way for the European isolates. Information only, not medical advice.

Key facts

  • 1093/infdis/jiab385.
  • Affiliations are the Mitchell Center for Alzheimer's Disease and Related Brain Disorders at the University of Texas McGovern Medical School in Houston (Pritzkow, Gorski, Ramirez, Soto), the Prion Research Center at Colorado State University (Telling) and the Norwegian Veterinary Institute, then OIE reference laboratory for CWD, at Aas (Benestad).
  • Six isolates were compared: whitetail deer, elk and mule deer from North America, and moose, reindeer and red deer from Norway, the Norwegian samples being pools of several brain regions per animal.
  • North American samples were diluted to match the misfolded prion protein content of the Norwegian moose sample (5.9 fold for whitetail deer, 21.7 fold for elk, 3.3 fold for mule deer), so that starting seed loads were comparable.
  • Spillover testing used one PMCA round of 144 cycles against sheep (ARQ), hamster, mouse, bovine and porcine substrates; human testing used a second round of 96 further cycles with human prion protein substrates carrying methionine or valine at codon 129.
  • Table 1 of the paper gives spillover scores of 9 (whitetail deer), 3 (elk), 6 (mule deer), 8 (red deer), 12 (reindeer) and 9 (moose), so the Norwegian reindeer isolate was the most promiscuous across non-human substrates.
  • The same table gives zoonotic scores of 6 for whitetail deer (2 with 129M plus 4 with 129V), 5 for mule deer, 4 for elk and 0 for each of the three Norwegian isolates.
  • No isolate converted human prion protein in the first round; the North American isolates did so only in the second round, and the Norwegian isolates produced no detectable human conversion at either round.
  • Substrate by substrate, whitetail deer and Norwegian reindeer were the best seeds for sheep prion protein, red deer and reindeer for hamster, and Norwegian moose for bovine prion protein; no isolate converted pig prion protein in round one, and mouse was a poor substrate for all.
  • The authors conclude that Norwegian and North American CWD prions correspond to different strains with distinct spillover and zoonotic potential, and suggest North American CWD may carry more human risk, possibly because it has circulated longer and stabilised.
  • Stated limits: PMCA does not model clearance, bioavailability or neuronal vulnerability, only a few samples were tested, only the sheep ARQ polymorphism was used, and the findings complement rather than replace animal bioassays.
  • Funding was NIH NIAID P01 AI077774, Norwegian Veterinary Institute project 12081 and Norwegian Environment Agency project 3201040004, with the funders stated to have had no role in the work; Soto and Pritzkow declare PMCA patents and a relationship with Amprion Inc, and the University of Texas System has licensed PMCA intellectual property to that company.
  • A 2023 review in Foods by Tranulis and Tryland describes the same experiment, notes that the Norwegian reindeer isolate converted sheep, bovine and hamster prion protein about as well as whitetail deer CWD, and concludes that most experimental data put the zoonotic risk of CWD very low while urging that exposure be kept to a minimum.
  • The Norwegian Scientific Committee for Food and Environment report 2021:08, commissioned by the Norwegian Food Safety Authority, judged the risk to people from handling or eating meat from CWD infected deer very low and asked for exposure to be limited, surveillance of human prion disease and reduction of CWD prevalence; its page does not mention PMCA or this study.
  • The Europe PMC record showed 29 citations when read on 21 October 2026.

Timeline

  1. 2021Manuscript received, 20 April.
  2. 2021VKM report 2021:08 on CWD and risk of transmission to humans published, 1 June.
  3. 2021Accepted 23 July and published online 24 July.
  4. 2022Printed in the February 2022 issue, J Infect Dis 225(3):542-551.
  5. 2023Tranulis and Tryland review citing the experiment published in Foods, 15 February.
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