title: Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy infection following passage in sheep.
abstract: The risk of the transmission of ruminant transmissible spongiform encephalopathy (TSE) to humans was thought to be low due to the lack of association between sheep scrapie and the incidence of human TSE. However, a single TSE agent strain has been shown to cause both bovine spongiform encephalopathy (BSE) and human vCJD, indicating that some ruminant TSEs are transmissible to humans. While the transmission of cattle BSE to humans in transgenic mouse models has been inefficient, indicating the presence of a significant transmission barrier between cattle and humans, BSE has been transmitted to a number of other species. Here, we aimed to further investigate the human transmission barrier following the passage of BSE in a sheep. Following inoculation with cattle BSE, gene-targeted transgenic mice expressing human PrP showed no clinical or pathological signs of TSE disease. However, following inoculation with an isolate of BSE that had been passaged through a sheep, TSE-associated vacuolation and proteinase K-resistant PrP deposition were observed in mice homozygous for the codon 129-methionine PRNP gene. This observation may be due to higher titers of the BSE agent in sheep or an increased susceptibility of humans to BSE prions following passage through a sheep. However, these data confirm that, contrary to previous predictions, it is possible that a sheep prion is transmissible to humans and that BSE from other species is a public health risk.
authors.affiliation: Neuropathogenesis Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin, Midlothian EH25 9PS, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Plinston
authors.forename: Patricia
authors.initials: P
authors.lastname: Hart
authors.forename: Angela
authors.initials: A
authors.lastname: Chong
authors.forename: Nora
authors.initials: N
authors.lastname: Hunter
authors.forename: James
authors.initials: J
authors.lastname: Foster
authors.forename: Pedro
authors.initials: P
authors.lastname: Piccardo
authors.forename: Jean C
authors.initials: JC
authors.lastname: Manson
authors.forename: Rona M
authors.initials: RM
authors.lastname: Barron
mesh_terms: D000818:Animals; D002417:Cattle; D007562:Creutzfeldt-Jakob Syndrome / Q000139:chemically induced*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D016643:Encephalopathy, Bovine Spongiform / Q000635:transmission*; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000096:biosynthesis* / Q000235:genetics*; D012608:Scrapie / Q000635:transmission*
chemical_list: D011328:Prions