title: Genotype-dependent molecular evolution of sheep bovine spongiform encephalopathy (BSE) prions in vitro affects their zoonotic potential.
abstract: Prion diseases are rare fatal neurological conditions of humans and animals, one of which (variant Creutzfeldt-Jakob disease) is known to be a zoonotic form of the cattle disease bovine spongiform encephalopathy (BSE). What makes one animal prion disease zoonotic and others not is poorly understood, but it appears to involve compatibility between the prion strain and the host prion protein sequence. Concerns have been raised that the United Kingdom sheep flock may have been exposed to BSE early in the cattle BSE epidemic and that serial BSE transmission in sheep might have resulted in adaptation of the agent, which may have come to phenotypically resemble scrapie while maintaining its pathogenicity for humans. We have modeled this scenario in vitro. Extrapolation from our results suggests that if BSE were to infect sheep in the field it may, with time and in some sheep genotypes, become scrapie-like at the molecular level. However, the results also suggest that if BSE in sheep were to come to resemble scrapie it would lose its ability to affect humans.
authors.affiliation: National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh, Edinburgh EH4 2XU, United Kingdom.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Krejciova
authors.affiliation: National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh, Edinburgh EH4 2XU, United Kingdom.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Barria
authors.affiliation: Scottish National Blood Transfusion Service, Edinburgh EH17 7QT, United Kingdom, and.
authors.forename: Michael
authors.initials: M
authors.lastname: Jones
authors.affiliation: National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh, Edinburgh EH4 2XU, United Kingdom.
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.affiliation: Animal Health and Veterinary Laboratories Agency, Lasswade, Edinburgh EH26 0PZ, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Jeffrey
authors.affiliation: Animal Health and Veterinary Laboratories Agency, Lasswade, Edinburgh EH26 0PZ, United Kingdom.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: González
authors.affiliation: National Creutzfeldt-Jakob Disease Research and Surveillance Unit, The University of Edinburgh, Edinburgh EH4 2XU, United Kingdom,. Electronic address: m.w.head@ed.ac.uk.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Head
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics / Q000635:transmission*; D019143:Evolution, Molecular; D005838:Genotype; D006031:Glycosylation; D006801:Humans; D011328:Prions / Q000235:genetics* / Q000378:metabolism; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D012608:Scrapie / Q000235:genetics / Q000635:transmission*; D034561:Sheep, Domestic; D015047:Zoonoses
chemical_list: D011328:Prions
keywords: Molecular Evolution; Prion; Prion Disease; Protein Conformation; Protein Misfolding; Protein Misfolding Cyclic Amplification; Sheep BSE; Zoonosis
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