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 resultedin effective methods to decide about the absence of BSE. In rare instances uncertainties remain due to assumptionsthat BSE, classical scrapie and CH1641–a rare scrapie variant–could occur as mixtures. In field samples including thosefrom fallen stock, triplex Western blotting analyses of variations in the molecular properties of the proteinase K resistantpart of the disease‑associated form of prion protein (PrPres) represents a powerful tool for quick discriminationpurposes. In this study we examined 7 deviant ovine field cases of scrapie for some typical molecular aspects of PrPresfound in CH1641‑scrapie, classical scrapie and BSE. One case was most close to scrapie with respect to molecular massof its non-glycosylated fraction and N-terminally located 12B2‑epitope content. Two cases were unlike classical scrapiebut too weak to differentiate between BSE or CH1641. The other 4 cases appeared intermediate between scrapie andCH1641 with a reduced molecular mass and 12B2‑epitope content, together with the characteristic presence of asecond PrPres population. The existence of these 2 PrPres populations was further confirmed through deglycosylation byPNGaseF. The findings indicate that discriminatory diagnosis between classical scrapie, CH1641 and BSE can remaininconclusive with current biochemical methods. Whether such intermediate cases represent mixtures of TSE strainsshould be further investigated e.g. in bioassays with rodent lines that are varying in their susceptibility or othertechniques suitable for strain typing