Biochemical Characterization of Prion Strains in Bank Voles

Prions exist as different strains exhibiting distinct disease phenotypes. Currently, the identification of prion strains is still based on biological strain typing in rodents. However, it has been shown that prion strains may be associated with distinct PrP(Sc) biochemical types. Taking advantage of the availability of several prion strains adapted to a novel rodent model, the bank vole, we investigated if any prion strain was actually associated with distinctive PrP(Sc) biochemical characteristics and if it was possible to univocally identify strains through PrP(Sc) biochemical phenotypes. We selected six different vole-adapted strains (three human-derived and three animal-derived) and analyzed PrP(Sc) from individual voles by epitope mapping of protease resistant core of PrP(Sc) (PrP(res)) and by conformational stability and solubility assay. Overall, we discriminated five out of six prion strains, while two different scrapie strains showed identical PrP(Sc) types. Our results suggest that the biochemical strain typing approach here proposed was highly discriminative, although by itself it did not allow us to identify all prion strains analyzed.