The bank vole (Myodes glareolus) as a sensitive bioassay for sheep scrapie.
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.
Di Bari
Michele Angelo
MA
Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Chianini
Francesca
F
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
Vaccari
Gabriele
G
Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Esposito
Elena
E
Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Conte
Michela
M
Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Eaton
Samantha L
SL
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
Hamilton
Scott
S
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
Finlayson
Jeanie
J
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
Steele
Philip J
PJ
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
Dagleish
Mark P
MP
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
Reid
Hugh W
HW
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
Bruce
Moira
M
Neuropathogenesis Unit, Roslin Institute, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK.
Jeffrey
Martin
M
Veterinary Laboratories Agency (VLA-Lasswade), Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
Agrimi
Umberto
U
Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Nonno
Romolo
R
Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
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
D018620:PrPSc Proteins; D011328:Prions; D010447:Peptide Hydrolases