Strain characterization of natural sheep scrapie and comparison with BSE

Abstract

Scrapie was transmitted to mice from ten sheep, collected in the UK between 1985 and 1994. As in previous natural scrapie transmissions, the results varied between scrapie sources in terms of the incidence of disease, incubation periods and neuropathology in challenged mice. This contrasted with the uniformity seen in transmissions of BSE to mice. The scrapie and BSE isolates were characterized further by serial passage in mice. Different TSE strains were isolated from each source according to the Sinc or PrP genotype of the mouse used for passage. The same two mousepassaged strains, 301C and 301V, were isolated from each of three BSE sources. Despite the variation seen in the primary transmissions of scrapie, relatively few mouse-passaged scrapie strains were isolated and these were distinct from the BSE-derived strains. The ME7 scrapie strain, which has often been isolated from independent sheep sources in the past, was identified in isolates from four of the sheep. However, a new distinct strain, 221C, was derived from a further four scrapie sheep. These results suggest that there is agent strain variation in natural scrapie in sheep and that the spectrum of strains present may have changed over the last 20 years. The tested sample is too small to come to any conclusions about whether the BSE strain is present in sheep, but the study provides a framework for further more extensive studies.

Prion agent diversity and species barrier

“…In reviewing the published history of these transmission data, initiated by Dickinson et al and pursued by Bruce et al, it appears that the considerable strain variations described at a point (up to 20 strains, [32,70]) might finally be restricted to a varying combination of three distinct strains, as far as UK field scrapie cases are concerned (20 isolates studied): ME7 and 87A in Prna mice, and 87V in Prn-b mice (Tab. I, [33,36,37] . 3.3).…”

“…I, [33,37,36,165]). The last two resulted from BSE transmission to Prn-a and b mice as mentioned above in Section 3.3 [35].It is also important to notice that a substantial proportion of scrapie isolates failed to transmit to mice, in particular the scrapie sources from sheep homozygous for the ARQ allele [36,37,97]. So far it has been impossible to derive mouse TSE agents from these sources.…”

The evidence of associations between prion protein genotype and production, reproduction, and health traits in sheep

“…The concern that bovine spongiform encephalopathy (BSE) may have entered the sheep population [34,47] and is not obviously distinguishable from classical scrapie [14] prompted the EU Commission Decision 2003/100/EC, which requires member states to implement a breeding programme for resistance to transmissible spongiform encephalopathies (TSE) in sheep. While the resistance status of a sheep flock to classical scrapie and BSE can be rapidly improved by selective breeding [5,23], the relative economic value of such selection must be considered in the context of all of the other breeding objectives in local, national, and international breeding plans.…”

Differentiating Prion Strains Using Dendrimers

“…301C and 301V are mouse adapted prion strains originally isolated from BSE infected cattle. [21] The other prion strains examined are all originally derived from scrapie in sheep. This difference in origin may explain the ability of the 301C and 301V prion strains to resist the denaturing effect of the dendrimers examined.…”