Infectious titres of sheep scrapie and bovine spongiform encephalopathy agents cannot be accurately predicted from quantitative laboratory test results.
It is widely accepted that abnormal forms of the prion protein (PrP) are the best surrogate marker for the infectious agent of prion diseases and, in practice, the detection of such disease-associated (PrP(d)) and/or protease-resistant (PrP(res)) forms of PrP is the cornerstone of diagnosis and surveillance of the transmissible spongiform encephalopathies (TSEs). Nevertheless, some studies question the consistent association between infectivity and abnormal PrP detection. To address this discrepancy, 11 brain samples of sheep affected with natural scrapie or experimental bovine spongiform encephalopathy were selected on the basis of the magnitude and predominant types of PrP(d) accumulation, as shown by immunohistochemical (IHC) examination; contra-lateral hemi-brain samples were inoculated at three different dilutions into transgenic mice overexpressing ovine PrP and were also subjected to quantitative analysis by three biochemical tests (BCTs). Six samples gave 'low' infectious titres (10⁶·⁵ to 10⁶·⁷ LD₅₀ g⁻¹) and five gave 'high titres' (10⁸·¹ to ≥ 10⁸·⁷ LD₅₀ g⁻¹) and, with the exception of the Western blot analysis, those two groups tended to correspond with samples with lower PrP(d)/PrP(res) results by IHC/BCTs. However, no statistical association could be confirmed due to high individual sample variability. It is concluded that although detection of abnormal forms of PrP by laboratory methods remains useful to confirm TSE infection, infectivity titres cannot be predicted from quantitative test results, at least for the TSE sources and host PRNP genotypes used in this study. Furthermore, the near inverse correlation between infectious titres and Western blot results (high protease pre-treatment) argues for a dissociation between infectivity and PrP(res).
Animal Health and Veterinary Laboratories Agency (AHVLA), AHVLA-Lasswade, Pentlands Science Park, Penicuick, Midlothian EH26 0PZ, UK.
Lorenzo
L
González
Animal Health and Veterinary Laboratories Agency (AHVLA), AHVLA-Weybridge, Addlestone, Surrey KT15 3NB, UK.
Leigh
L
Thorne
Animal Health and Veterinary Laboratories Agency (AHVLA), AHVLA-Lasswade, Pentlands Science Park, Penicuick, Midlothian EH26 0PZ, UK.
Martin
M
Jeffrey
Animal Health and Veterinary Laboratories Agency (AHVLA), AHVLA-Lasswade, Pentlands Science Park, Penicuick, Midlothian EH26 0PZ, UK.
Stuart
S
Martin
Animal Health and Veterinary Laboratories Agency (AHVLA), AHVLA-Weybridge, Addlestone, Surrey KT15 3NB, UK.
John
J
Spiropoulos
Animal Health and Veterinary Laboratories Agency (AHVLA), AHVLA-Weybridge, Addlestone, Surrey KT15 3NB, UK.
Katy E
KE
Beck
Animal Health and Veterinary Laboratories Agency (AHVLA), AHVLA-Weybridge, Addlestone, Surrey KT15 3NB, UK.
Richard W
RW
Lockey
Animal Health and Veterinary Laboratories Agency (AHVLA), AHVLA-Weybridge, Addlestone, Surrey KT15 3NB, UK.
Christopher M
CM
Vickery
Animal Health and Veterinary Laboratories Agency (AHVLA), AHVLA-Weybridge, Addlestone, Surrey KT15 3NB, UK.
Thomas
T
Holder
Animal Health and Veterinary Laboratories Agency (AHVLA), AHVLA-Weybridge, Addlestone, Surrey KT15 3NB, UK.
Linda
L
Terry
D000818:Animals; D001681:Biological Assay / Q000379:methods; D001921:Brain; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D011328:Prions / Q000235:genetics* / Q000472:pathogenicity*; D012608:Scrapie; D012756:Sheep
D011328:Prions