title: Molecular assessment of the potential transmissibilities of BSE and scrapie to humans.
abstract: More than a million cattle infected with bovine spongiform encephalopathy (BSE) may have entered the human food chain. Fears that BSE might transmit to man were raised when atypical cases of Creutzfeldt-Jakob disease (CJD), a human transmissible spongiform encephalopathy (TSE), emerged in the UK. In BSE and other TSE diseases, the conversion of the protease-sensitive host prion protein (PrP-sen) to a protease-resistant isoform (PrP-res) is an important event in pathogenesis. Biological aspects of TSE diseases are reflected in the specificities of in vitro PrP conversion reactions. Here we show that there is a correlation between in vitro conversion efficiencies and known transmissibilities of BSE, sheep scrapie and CJD. On this basis, we used an in vitro system to gauge the potential transmissibility of scrapie and BSE to humans. We found limited conversion of human PrP-sen to PrP-res driven by PrP-res associated with both scrapie (PrP[Sc]) and BSE (PrP[BSE]). The efficiencies of these heterologous conversion reactions were similar but much lower than those of relevant homologous conversions. Thus the inherent ability of these infectious agents of BSE and scrapie to affect humans following equivalent exposure may be finite but similarly low.
authors.affiliation: Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Raymond
authors.forename: J
authors.initials: J
authors.lastname: Hope
authors.forename: D A
authors.initials: DA
authors.lastname: Kocisko
authors.forename: S A
authors.initials: SA
authors.lastname: Priola
authors.forename: L D
authors.initials: LD
authors.lastname: Raymond
authors.forename: A
authors.initials: A
authors.lastname: Bossers
authors.forename: J
authors.initials: J
authors.lastname: Ironside
authors.forename: R G
authors.initials: RG
authors.lastname: Will
authors.forename: S G
authors.initials: SG
authors.lastname: Chen
authors.forename: R B
authors.initials: RB
authors.lastname: Petersen
authors.forename: P
authors.initials: P
authors.lastname: Gambetti
authors.forename: R
authors.initials: R
authors.lastname: Rubenstein
authors.forename: M A
authors.initials: MA
authors.lastname: Smits
authors.forename: P T
authors.initials: PT
authors.lastname: Lansbury
authors.forename: B
authors.initials: B
authors.lastname: Caughey
mesh_terms: D000818:Animals; D002417:Cattle; D002474:Cell-Free System; D007562:Creutzfeldt-Jakob Syndrome / Q000635:transmission; D006224:Cricetinae; D004198:Disease Susceptibility; D016643:Encephalopathy, Bovine Spongiform / Q000635:transmission*; D019286:Endopeptidase K / Q000378:metabolism; D006801:Humans; D008647:Mesocricetus; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D018620:PrPSc Proteins / Q000378:metabolism*; D011328:Prions / Q000378:metabolism; D012608:Scrapie / Q000635:transmission*; D012756:Sheep; D013045:Species Specificity; D014407:Tumor Cells, Cultured; D015047:Zoonoses / Q000635:transmission*
chemical_list: D009419:Nerve Tissue Proteins; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions; D019286:Endopeptidase K