The bank vole (Myodes glareolus) as a sensitive bioassay for sheep scrapie

• Published in: Journal of general virology 2008-12, Vol.89 (12), p.2975-2985
• Main Authors: Di Bari, Michele Angelo, Chianini, Francesca, Vaccari, Gabriele, Esposito, Elena, Conte, Michela, Eaton, Samantha L, Hamilton, Scott, Finlayson, Jeanie, Steele, Philip J, Dagleish, Mark P, Reid, Hugh W, Bruce, Moira, Jeffrey, Martin, Agrimi, Umberto, Nonno, Romolo
• Format: Article
• Language: English
• Subjects: Animals; Arvicolinae - metabolism; Biological and medical sciences; Brain - metabolism; Disease Models, Animal; Disease Susceptibility; Fundamental and applied biological sciences. Psychology; Mice; Mice, Inbred C57BL; Microbiology; Miscellaneous; Myodes; Non conventional transmissible agents; Palatine Tonsil - metabolism; Peptide Hydrolases - pharmacology; Prions - genetics; Prions - metabolism; Prions - pathogenicity; PrPSc Proteins - drug effects; PrPSc Proteins - metabolism; PrPSc Proteins - pathogenicity; Scrapie - mortality; Scrapie - pathology; Scrapie - transmission; Sheep; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.2008/005520-0

1 Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy 2 Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK 3 Neuropathogenesis Unit, Roslin Institute, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK 4 Veterinary Laboratories Agency (VLA-Lasswade), Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK Correspondence Romolo Nonno romolo.nonno{at}iss.it 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 ID 50 U g –1 and 10 5.8 ID 50 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 PrP Sc molecular characteristics, strain and prion titre in the brain and tonsil of the same scrapie-affected sheep. We found that protease-resistant PrP Sc fragments (PrP res ) 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. ID 50 U g –1 , i.e. fivefold less than the brain. This compared well with the relative PrP res 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 PrP Sc -based estimate of scrapie infectivity in sheep tissues could be achieved by combining sensitive PrP res detection methods and bioassay in voles. Published online ahead of print on 30 September 2008 as DOI 10.1099/vir.0.2008/005520-0.