title: Further characterisation of transmissible spongiform encephalopathy phenotypes after inoculation of cattle with two temporally separated sources of sheep scrapie from Great Britain.
abstract: BACKGROUND
  The infectious agent responsible for the bovine spongiform encephalopathy (BSE) epidemic in Great Britain is a transmissible spongiform encephalopathy (TSE) strain with uniform properties but the origin of this strain remains unknown. Based on the hypothesis that classical BSE may have been caused by a TSE strain present in sheep, cattle were inoculated intracerebrally with two different pools of brains from scrapie-affected sheep sourced prior to and during the BSE epidemic to investigate resulting disease phenotypes and characterise their causal agents by transmission to rodents.
  
  
  RESULTS
  As reported in 2006, intracerebral inoculation of cattle with pre-1975 and post-1990 scrapie brain pools produced two distinct disease phenotypes, which were unlike classical BSE. Subsequent to that report none of the remaining cattle, culled at 10 years post inoculation, developed a TSE. Retrospective Western immunoblot examination of the brains from TSE cases inoculated with the pre-1975 scrapie pool revealed a molecular profile similar to L-type BSE. The inoculation of transgenic mice expressing the bovine, ovine, porcine, murine or human prion protein gene and bank voles with brains from scrapie-affected cattle did not detect classical or atypical BSE strains but identified two previously characterised scrapie strains of sheep.
  
  
  CONCLUSIONS
  Characterisation of the causal agents of disease resulting from exposure of cattle to naturally occurring scrapie agents sourced in Great Britain did not reveal evidence of classical or atypical BSE, but did identify two distinct previously recognised strains of scrapie. Although scrapie was still recognizable upon cattle passage there were irreconcilable discrepancies between the results of biological strain typing approaches and molecular profiling methods, suggesting that the latter may not be appropriate for the identification and differentiation of atypical, particularly L-type, BSE agents from cattle experimentally infected with a potential mixture of classical scrapie strains from sheep sources.
authors.affiliation: Specialist Scientific Support Department, Animal and Plant Health Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK. Timm.Konold@apha.gsi.gov.uk.
authors.forename: Timm
authors.initials: T
authors.lastname: Konold
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità (ISS), Viale Regina Elena 299, 00161, Rome, Italy. romolo.nonno@iss.it.
authors.forename: Romolo
authors.initials: R
authors.lastname: Nonno
authors.affiliation: Pathology Department, Animal and Plant Health Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK. John.Spiropoulos@apha.gsi.gov.uk.
authors.forename: John
authors.initials: J
authors.lastname: Spiropoulos
authors.affiliation: Prion Unit, Virology Department, Animal and Plant Health Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK. Melanie.Chaplin@apha.gsi.gov.uk.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Chaplin
authors.affiliation: Prion Unit, Virology Department, Animal and Plant Health Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK. stackmichael@hotmail.co.uk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stack
authors.affiliation: Pathology Department, Animal and Plant Health Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK. Steve.Hawkins@apha.gsi.gov.uk.
authors.forename: Steve A C
authors.initials: SA
authors.lastname: Hawkins
authors.affiliation: Specialist Scientific Support Department, Animal and Plant Health Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK. Saira.Cawthraw@apha.gsi.gov.uk.
authors.forename: Saira
authors.initials: S
authors.lastname: Cawthraw
authors.affiliation: Formerly Epidemiology Department, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK. johnwilesmith@barrscourt.plus.com.
authors.forename: John W
authors.initials: JW
authors.lastname: Wilesmith
authors.affiliation: Formerly Neuropathology, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK. geraldwells5@btinternet.com.
authors.forename: Gerald A H
authors.initials: GA
authors.lastname: Wells
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità (ISS), Viale Regina Elena 299, 00161, Rome, Italy. umberto.agrimi@iss.it.
authors.forename: Umberto
authors.initials: U
authors.lastname: Agrimi
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità (ISS), Viale Regina Elena 299, 00161, Rome, Italy. michele.dibari@iss.it.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Di Bari
authors.affiliation: UMR INRA-ENVT 1225, Interactions Hôte Agent Pathogène, École Nationale Vétérinaire de Toulouse, 31076, Toulouse Cedex 3, France. o.andreoletti@envt.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Andréoletti
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain. espinosa.juan@inia.es.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Espinosa
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain. patriciaaguilar@ucsd.edu.
authors.forename: Patricia
authors.initials: P
authors.lastname: Aguilar-Calvo
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain. jmtorres@inia.es.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Torres
mesh_terms: D000818:Animals; D003411:Arvicolinae; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism* / Q000473:pathology / Q000635:transmission; D015870:Gene Expression; D006801:Humans; D007276:Injections, Intraventricular; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D018620:PrPSc Proteins / Q000235:genetics* / Q000378:metabolism; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology / Q000635:transmission; D012756:Sheep; D034561:Sheep, Domestic; D013997:Time Factors; D006113:United Kingdom
chemical_list: D018620:PrPSc Proteins