This page summarises how strains are classified in two published studies. It does not say where isolates are held or how to obtain them. Custodians set their own conditions, and national and institutional biosafety rules apply to any work. Each study was read in part, about 100,000 characters of 115,000 for the scrapie paper.
How many classical scrapie strains are there?
Marin-Moreno and colleagues (Veterinary Research, 2021) transmitted goat and sheep scrapie isolates into two transgenic mouse models, TgGoat-ARQ and TgBov, in a second passage, which they say overcame the species barrier seen at first passage. They classified isolates by incubation time, the Western blot signature of protease-resistant PrP (21 or 19 kDa) and, in TgBov mice, transmission behaviour. They grouped isolates in four categories:
| Category | Isolates described |
|---|---|
| I | Italian goat and sheep isolates, and one French goat isolate with partial features |
| II | Several goat and sheep isolates giving a 21 kDa signature in TgGoat-ARQ and 19 kDa in TgBov mice |
| III | Isolates including UKB2, Portuguese sheep isolates and CH1641 |
| IV | Several goat isolates and sheep isolate PS83, with slow transmission in both models |
The authors propose that at least four classical scrapie strains circulate in Europe, and that the same strains occur in goats and sheep. Some isolates appeared to hold more than one strain. UKA2 gave either signature in TgGoat-ARQ mice, and N3 gave two agents with short and long incubation in TgBov mice. They could not tell whether both were present in the original material or one arose during passage. The authors note that TgBov mice express PrP at very high levels, and that strain shift from overexpression cannot be fully excluded.
On human relevance they state that the zoonotic potential of scrapie is not fully deciphered. The study did not test human PrP models, so it does not address human risk directly. The scrapie strains tested appeared clearly distinct from classical BSE in these models.
Do Norwegian and North American CWD isolates differ?
Pritzkow and colleagues (Journal of Infectious Diseases, 2022) compared isolates from whitetail deer, mule deer and elk in North America with reindeer, red deer and moose from Norway. They used protein misfolding cyclic amplification, an in vitro method, to test conversion of normal prion protein from mouse, hamster, sheep, cattle, pig and human.
Summed spillover indices across non-human substrates were reindeer 12, whitetail deer 9, moose 9, red deer 8, mule deer 6 and elk 3. The authors describe the Norwegian isolates as generally better able to cross species barriers, with whitetail deer an exception. For human prion protein, tested over two rounds with 129M and 129V, the North American isolates converted it (whitetail deer 6, mule deer 5, elk 4) and none of the Norwegian isolates did. They conclude that Norwegian and North American CWD correspond to different strains with distinct spillover and zoonotic potentials.
The authors state the limits: an in vitro method does not capture clearance, bioavailability or selective neuronal vulnerability and does not replace infectivity bioassays, and few samples were tested. The sheep substrate carried only the ARQ polymorphism. These findings do not establish risk to people. See CWD zoonotic risk and chronic wasting disease.
What defines a strain?
Manka and colleagues define strains as transmissible variants that produce distinct clinicopathological phenotypes in the same host, probably encoded by distinct misfolded PrP conformations. See prion strains.
What is not known?
Whether the categories above hold with more isolates, how mixtures arise, and which strains can infect humans. Related pages are antibodies and reagents, models, reference materials and the resources hub.
Sources for this page
- Marin-Moreno A and others. Classical scrapie in small ruminants is caused by at least four different prion strains. Vet Res 2021;52:57 (PMC8048364)
- Pritzkow S and others. North American and Norwegian chronic wasting disease prions exhibit different potential for interspecies transmission and zoonotic risk. J Infect Dis 2022;225(3):542-551 (PMC8807243)
- Manka SW, Wenborn A, Collinge J, Wadsworth JDF. Prion strains viewed through the lens of cryo-EM. Cell Tissue Res 2023;392(1):167-178 (PMC10113314)