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Different prion disease phenotypes result from inoculation of cattle with two temporally separated sources of sheep scrapie from Great Britain.

Konold T, Lee YH, Stack MJ, Horrocks C, Green RB, Chaplin M, Simmons MM, Hawkins SA, Lockey R, Spiropoulos J, Wilesmith JW, Wells GA - BMC Vet. Res. (2006)

Bottom Line: Disease 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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, UK. t.konold@vla.defra.gsi.gov.uk

ABSTRACT

Background: 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. 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.

Results: Disease 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.

Conclusion: The 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.

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Western immunoblot with monoclonal antibody P4 on caudal medulla samples from cattle in the pre-1975 and post-1990 group.
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Figure 5: Western immunoblot with monoclonal antibody P4 on caudal medulla samples from cattle in the pre-1975 and post-1990 group.

Mentions: All clinically affected cattle inoculated with scrapie tested positive for PrPres. However, the molecular profiles obtained with the VLA hybrid WB technique differed between the two groups, and none of the molecular profiles obtained were identical to the scrapie or BSE controls (Figures 4 and 5). Immunoblotting of caudal medulla from the eight pre-1975 challenged cattle gave a uniform molecular profile for all animals in the group. Using monoclonal antibody (mAb) 6H4, an unglycosylated band of lower molecular mass than the natural scrapie control sample was obtained and with mAb P4 there was no immuno-reaction. This was similar to the corresponding molecular profile obtained with these two mAbs for the natural cattle BSE control sample. However, although the molecular mass of the unglycosylated band was not significantly lower than that of the BSE control (approximately 0.2 kDa; p = 0.211) the monoglycosylated band (approximately 0.3 kDa; p = 0.008) and the diglycosylated band (approximately 0.5 kDa; p = 0.001) were significantly lower.


Different prion disease phenotypes result from inoculation of cattle with two temporally separated sources of sheep scrapie from Great Britain.

Konold T, Lee YH, Stack MJ, Horrocks C, Green RB, Chaplin M, Simmons MM, Hawkins SA, Lockey R, Spiropoulos J, Wilesmith JW, Wells GA - BMC Vet. Res. (2006)

Western immunoblot with monoclonal antibody P4 on caudal medulla samples from cattle in the pre-1975 and post-1990 group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1636635&req=5

Figure 5: Western immunoblot with monoclonal antibody P4 on caudal medulla samples from cattle in the pre-1975 and post-1990 group.
Mentions: All clinically affected cattle inoculated with scrapie tested positive for PrPres. However, the molecular profiles obtained with the VLA hybrid WB technique differed between the two groups, and none of the molecular profiles obtained were identical to the scrapie or BSE controls (Figures 4 and 5). Immunoblotting of caudal medulla from the eight pre-1975 challenged cattle gave a uniform molecular profile for all animals in the group. Using monoclonal antibody (mAb) 6H4, an unglycosylated band of lower molecular mass than the natural scrapie control sample was obtained and with mAb P4 there was no immuno-reaction. This was similar to the corresponding molecular profile obtained with these two mAbs for the natural cattle BSE control sample. However, although the molecular mass of the unglycosylated band was not significantly lower than that of the BSE control (approximately 0.2 kDa; p = 0.211) the monoglycosylated band (approximately 0.3 kDa; p = 0.008) and the diglycosylated band (approximately 0.5 kDa; p = 0.001) were significantly lower.

Bottom Line: Disease 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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, UK. t.konold@vla.defra.gsi.gov.uk

ABSTRACT

Background: 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. 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.

Results: Disease 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.

Conclusion: The 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.

Show MeSH
Related in: MedlinePlus