Abstract
IntroductionScrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSEs) which naturally affect small and large ruminants respectively. However, small ruminants, which are susceptible to BSE under experimental conditions, have been exposed to the same or similar contaminated food additives as cattle. To date two natural cases of BSE in small ruminants have been reported. As a result surveillance projects, combined with appropriate control measures, have been established throughout the European Union (EU) to minimize the overall incidence of small ruminant TSEs. Although BSE can be differentiated from classical scrapie (subsequently referred to as scrapie) if appropriate discriminatory tests are applied, the value of these tests in BSE/scrapie co-infection scenarios has not been evaluated fully. Mouse bioassay is regarded as the gold standard regarding differentiation of distinct TSE strains and has been used as to resolve TSE cases were laboratory tests produced equivocal results. However, the ability of this method to discriminate TSE strains when they co-exist has not been examined systematically. To address this issue we prepared in vitro mixtures of ovine BSE and scrapie and used them to challenge RIII, C57BL/6 and VM mice.ResultsDisease phenotype analysis in all three mouse lines indicated that most phenotypic parameters (attack rates, incubation periods, lesion profiles and Western blots) were compatible with scrapie phenotypes as were immunohistochemistry (IHC) data from RIII and C57BL/6 mice. However, in VM mice that were challenged with BSE/scrapie mixtures a single BSE-associated IHC feature was identified, indicating the existence of BSE in animals where the scrapie phenotype was dominant.ConclusionsWe conclude that wild type mouse bioassay is of limited value in detecting BSE in the presence of scrapie particularly if the latter is in relative excess.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0194-2) contains supplementary material, which is available to authorized users.
Highlights
Scrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSEs) which naturally affect small and large ruminants respectively
Disease phenotype analysis in all three mouse lines indicated that most phenotypic parameters were compatible with scrapie phenotypes as were immunohistochemistry (IHC) data from RIII and C57BL/6 mice
We conclude that wild type mouse bioassay is of limited value in detecting BSE in the presence of scrapie if the latter is in relative excess
Summary
Scrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSEs) which naturally affect small and large ruminants respectively. Experimental challenge of small ruminants with BSE proved that they are susceptible, resulting in a disease with clinical signs that are indistinguishable from those caused by scrapie [10,11]. Such studies have provided invaluable materials for the development of immunochemical and immunohistochemical discriminatory tests that have the ability to differentiate between BSE and scrapie [12,13,14,15,16,17]
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