Sheep prions with molecular properties intermediate between classical scrapie, BSE and CH1641-scrapie

Efforts to differentiate bovine spongiform encephalopathy (BSE) from scrapie in prion infected sheep have resulted<br/>in effective methods to decide about the absence of BSE. In rare instances uncertainties remain due to assumptions<br/>that BSE, classical scrapie and CH1641–a rare scrapie variant–could occur as mixtures. In field samples including those<br/>from fallen stock, triplex Western blotting analyses of variations in the molecular properties of the proteinase K resistant<br/>part of the disease‑associated form of prion protein (PrPres) represents a powerful tool for quick discrimination<br/>purposes. In this study we examined 7 deviant ovine field cases of scrapie for some typical molecular aspects of PrPres<br/>found in CH1641‑scrapie, classical scrapie and BSE. One case was most close to scrapie with respect to molecular mass<br/>of its non-glycosylated fraction and N-terminally located 12B2‑epitope content. Two cases were unlike classical scrapie<br/>but too weak to differentiate between BSE or CH1641. The other 4 cases appeared intermediate between scrapie and<br/>CH1641 with a reduced molecular mass and 12B2‑epitope content, together with the characteristic presence of a<br/>second PrPres population. The existence of these 2 PrPres populations was further confirmed through deglycosylation by<br/>PNGaseF. The findings indicate that discriminatory diagnosis between classical scrapie, CH1641 and BSE can remain<br/>inconclusive with current biochemical methods. Whether such intermediate cases represent mixtures of TSE strains<br/>should be further investigated e.g. in bioassays with rodent lines that are varying in their susceptibility or other<br/>techniques suitable for strain typing