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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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Glycoform profiles for cattle of the pre-1975 and post-1990 group compared to scrapie and BSE. The glycoform profiles are given as the percentage signal (mean with standard error) of the diglycosylated protein band plotted against that of the monoglycosylated band. The outlier PG152/02 of the post-1990 group is included.
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Figure 9: Glycoform profiles for cattle of the pre-1975 and post-1990 group compared to scrapie and BSE. The glycoform profiles are given as the percentage signal (mean with standard error) of the diglycosylated protein band plotted against that of the monoglycosylated band. The outlier PG152/02 of the post-1990 group is included.

Mentions: The mean glycoform ratios obtained from individual brain samples from cattle of the pre-1975 (n = 7) and post-1990 (n = 6, included is the outlier PG152/02) group were compared to those obtained from a natural BSE case and a natural scrapie case (Figure 9). The results show that the glycoform ratio for the BSE control field sample (60.5:27.5) was separate from those obtained for the natural sheep scrapie control sample (45.2:36.8) and all other samples from the two inoculated groups (ranging between 52.7:34.3 and 38.0:39.3). The glycoform ratios for caudal medulla and brainstem tissues from the outliers of the post-1990 group (PG152/05 and PG512/05) were separate from the BSE control and were clustered close to the ratio obtained for the sheep scrapie control (Figure 10).


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)

Glycoform profiles for cattle of the pre-1975 and post-1990 group compared to scrapie and BSE. The glycoform profiles are given as the percentage signal (mean with standard error) of the diglycosylated protein band plotted against that of the monoglycosylated band. The outlier PG152/02 of the post-1990 group is included.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: Glycoform profiles for cattle of the pre-1975 and post-1990 group compared to scrapie and BSE. The glycoform profiles are given as the percentage signal (mean with standard error) of the diglycosylated protein band plotted against that of the monoglycosylated band. The outlier PG152/02 of the post-1990 group is included.
Mentions: The mean glycoform ratios obtained from individual brain samples from cattle of the pre-1975 (n = 7) and post-1990 (n = 6, included is the outlier PG152/02) group were compared to those obtained from a natural BSE case and a natural scrapie case (Figure 9). The results show that the glycoform ratio for the BSE control field sample (60.5:27.5) was separate from those obtained for the natural sheep scrapie control sample (45.2:36.8) and all other samples from the two inoculated groups (ranging between 52.7:34.3 and 38.0:39.3). The glycoform ratios for caudal medulla and brainstem tissues from the outliers of the post-1990 group (PG152/05 and PG512/05) were separate from the BSE control and were clustered close to the ratio obtained for the sheep scrapie control (Figure 10).

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