Genotype-dependent Molecular Evolution of Sheep Bovine Spongiform Encephalopathy (BSE) Prions in Vitro Affects Their Zoonotic Potential

Zuzana Krejciova, Marcelo A Barria, Michael Jones, James W Ironside, Martin Jeffrey, Lorenzo González, Mark W Head

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)26075-26088
Number of pages14
JournalJournal of Biological Chemistry
Volume289
Issue number38
DOIs
Publication statusPublished - 19 Sep 2014

Keywords

  • CREUTZFELDT-JAKOB-DISEASE
  • MISFOLDING CYCLIC AMPLIFICATION
  • INFECTED SHEEP
  • ORAL-TRANSMISSION
  • PRP ACCUMULATION
  • GREAT-BRITAIN
  • BRITISH SHEEP
  • SCRAPIE
  • PROTEIN
  • VARIANT

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