title: The bank vole (Myodes glareolus) as a sensitive bioassay for sheep scrapie.
abstract: Despite intensive studies on sheep scrapie, a number of questions remain unanswered, such as the natural mode of transmission and the amount of infectivity which accumulates in edible tissues at different stages of scrapie infection. Studies using the mouse model proved to be useful for recognizing scrapie strain diversity, but the low sensitivity of mice to some natural scrapie isolates hampered further investigations. To investigate the sensitivity of bank voles (Myodes glareolus) to scrapie, we performed end-point titrations from two unrelated scrapie sources. Similar titres [10(5.5) ID50 U g(-1) and 10(5.8) ID50 U g(-1), both intracerebrally (i.c.)] were obtained, showing that voles can detect infectivity up to 3-4 orders of magnitude lower when compared with laboratory mice. We further investigated the relationships between PrPSc molecular characteristics, strain and prion titre in the brain and tonsil of the same scrapie-affected sheep. We found that protease-resistant PrPSc fragments (PrPres) from brain and tonsil had different molecular features, but induced identical disease phenotypes in voles. The infectivity titre of the tonsil estimated by incubation time assay was 10(4.8) i.c. ID50 U g(-1), i.e. fivefold less than the brain. This compared well with the relative PrPres content, which was 8.8-fold less in tonsil than in brain. Our results suggest that brain and tonsil harboured the same prion strain showing different glycoprofiles in relation to the different cellular/tissue types in which it replicated, and that a PrPSc-based estimate of scrapie infectivity in sheep tissues could be achieved by combining sensitive PrPres detection methods and bioassay in voles.
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Michele Angelo
authors.initials: MA
authors.lastname: Di Bari
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Chianini
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Vaccari
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Conte
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Eaton
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
authors.forename: Scott
authors.initials: S
authors.lastname: Hamilton
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
authors.forename: Jeanie
authors.initials: J
authors.lastname: Finlayson
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Steele
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Dagleish
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
authors.forename: Hugh W
authors.initials: HW
authors.lastname: Reid
authors.affiliation: Neuropathogenesis Unit, Roslin Institute, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK.
authors.forename: Moira
authors.initials: M
authors.lastname: Bruce
authors.affiliation: Veterinary Laboratories Agency (VLA-Lasswade), Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Jeffrey
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Agrimi
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Romolo
authors.initials: R
authors.lastname: Nonno
mesh_terms: D000818:Animals; D003411:Arvicolinae / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D051379:Mice; D008810:Mice, Inbred C57BL; D014066:Palatine Tonsil / Q000378:metabolism; D010447:Peptide Hydrolases / Q000494:pharmacology; D018620:PrPSc Proteins / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D011328:Prions / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D012608:Scrapie / Q000401:mortality / Q000473:pathology / Q000635:transmission; D012756:Sheep
chemical_list: D018620:PrPSc Proteins; D011328:Prions; D010447:Peptide Hydrolases