Experimental transmission of atypical scrapie to sheep

Abstract

Background: Active surveillance for transmissible spongiform encephalopathies in small ruminants has been an EU regulatory requirement since 2002. A number of European countries have subsequently reported cases of atypical scrapie, similar to previously published cases from Norway, which have pathological and molecular features distinct from classical scrapie. Most cases have occurred singly in flocks, associated with genotypes considered to be more resistant to classical disease. Experimental transmissibility of such isolates has been reported in certain ovinised transgenic mice, but has not previously been reported in the natural host. Information on the transmissibility of this agent is vital to ensuring that disease control measures are effective and proportionate.

Results: This report presents the successful experimental transmission, in 378 days, of atypical scrapie to a recipient sheep of homologous genotype with preservation of the pathological and molecular characteristics of the donor. This isolate also transmitted to ovinised transgenic mice (Tg338) with a murine phenotype indistinguishable from that of Nor 98.

Conclusion: This result strengthens the opinion that these cases result from a distinct strain of scrapie agent, which is potentially transmissible in the natural host under field conditions.

Figure 1

BioRad Western Blot (10 min Detection). 15 μl of sample is loaded in each lane, giving a tissue equivalent of 0.02 g. Each sample is run in duplicate in adjacent lanes. Lanes 1 and 2 UK passive surveillance atypical scrapie (ARQ/AHQ; cortex). Lanes 3 and 4 UK passive surveillance atypical scrapie (AHQ/ARR; cortex). Lanes 5 and 6 UK active surveillance atypical scrapie (AHQ/ARR; medulla). Lanes 7 and 8 Donor sheep. UK active surveillance atypical scrapie (AHQ/AHQ; medulla). Lanes 9 and 10 Recipient sheep. Experimental atypical scrapie (AHQ/AHQ; medulla). Lane 11 UK classical scrapie positive control (VRQ/VRQ; medulla). Lane 12 Swedish Nor98 positive control (kindly supplied by Dr D Gavier-Widen, SVA, Sweden). Lane 13 UK bovine BSE positive active surveillance case control (brainstem). Lanes M Molecular mass markers.

Figure 2

Distribution and type of PrP immunolabelling in the donor (A) and the recipient sheep (B). Red = fine particulate staining of the neuropil. Green = coarse particulate/globular staining in the white matter. i) medulla oblongata (level of the obex); ii) rostral medulla/cerebellum; iii) caudal midbrain; iv) rostral midbrain; v) thalamus/occipital cortex/hippocampus; vi) rostral thalamus/hypothalamus/parietal cortex; vii) frontal cortex/basal ganglion.