Abstract
BackgroundGiven the theoretical proposal that bovine spongiform encephalopathy (BSE) could have originated from sheep scrapie, this study investigated the pathogenicity for cattle, by intracerebral (i.c.) inoculation, of two pools of scrapie agents sourced in Great Britain before and during the BSE epidemic.Two groups of ten cattle were each inoculated with pools of brain material from sheep scrapie cases collected prior to 1975 and after 1990. Control groups comprised five cattle inoculated with sheep brain free from scrapie, five cattle inoculated with saline, and for comparison with BSE, naturally infected cattle and cattle i.c. inoculated with BSE brainstem homogenate from a parallel study. Phenotypic characterisation of the disease forms transmitted to cattle was conducted by morphological, immunohistochemical, biochemical and biological methods.ResultsDisease occurred in 16 cattle, nine inoculated with the pre-1975 inoculum and seven inoculated with the post-1990 inoculum, with four cattle still alive at 83 months post challenge (as at June 2006). The different inocula produced predominantly two different disease phenotypes as determined by histopathological, immunohistochemical and Western immunoblotting methods and biological characterisation on transmission to mice, neither of which was identical to BSE. Whilst the disease presentation was uniform in all scrapie-affected cattle of the pre-1975 group, the post-1990 inoculum produced a more variable disease, with two animals sharing immunohistochemical and molecular profile characteristics with animals in the pre-1975 group.ConclusionThe study has demonstrated that cattle inoculated with different pooled scrapie sources can develop different prion disease phenotypes, which were not consistent with the phenotype of BSE of cattle and whose isolates did not have the strain typing characteristics of the BSE agent on transmission to mice.
Highlights
Given the theoretical proposal that bovine spongiform encephalopathy (BSE) could have originated from sheep scrapie, this study investigated the pathogenicity for cattle, by intracerebral (i.c.) inoculation, of two pools of scrapie agents sourced in Great Britain before and during the BSE epidemic.Two groups of ten cattle were each inoculated with pools of brain material from sheep scrapie cases collected prior to 1975 and after 1990
Strain typing of transmissible spongiform encephalopathy (TSE) isolates in mice from cattle, exotic ruminant species and domestic cats, of isolates of experimental BSE in sheep, goats and pigs [3,4] indicate the unique singularity of the BSE agent in Great Britain (GB), its apparent dissimilarity to isolates of natural scrapie of sheep, and its stability on natural or experimental single passage in the several species
As well as vacuolation within the brain, all TSEs are characterised by the accumulation of abnormal prion protein (PrPSc) in the central nervous system
Summary
Given the theoretical proposal that bovine spongiform encephalopathy (BSE) could have originated from sheep scrapie, this study investigated the pathogenicity for cattle, by intracerebral (i.c.) inoculation, of two pools of scrapie agents sourced in Great Britain before and during the BSE epidemic. Two groups of ten cattle were each inoculated with pools of brain material from sheep scrapie cases collected prior to 1975 and after 1990. Bovine spongiform encephalopathy (BSE) is a progressive and fatal neurological disease of cattle, which was first discovered in Great Britain (GB) in 1986 [1]. It is hypothesised that the cattle-adapted BSE agent originated either from sheep scrapie, the transmission resulting directly in clinical disease, or from cattle with a scrapie-like disease that was present endemically in cattle at a low level prior to the epidemic [2]. Neuropathological studies profiling vacuolar changes in BSE [5,6] have provided evidence of the single phenotype of BSE in GB and allow comparisons to be made with possible other TSE phenotypes in cattle caused by different agent strains
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