Prion Protein Glycosylation Is Not Required for Strain-Specific Neurotropism

Abstract

In this study, we tested the hypothesis that the glycosylation of the pathogenic isoform of the prion protein (PrP ^Sc ) might encode the selective neurotropism of prion strains. We prepared unglycosylated cellular prion protein (PrP ^C ) substrate molecules from normal mouse brain by treatment with PNGase F and used reconstituted serial protein cyclic misfolding amplification reactions to produce RML and 301C mouse prions containing unglycosylated PrP ^Sc molecules. Both RML- and 301C-derived prions containing unglycosylated PrP ^Sc molecules were infectious to wild-type mice, and neuropathological analysis showed that mice inoculated with these samples maintained strain-specific patterns of PrP ^Sc deposition and neuronal vacuolation. These results show that PrP ^Sc glycosylation is not necessary for strain-dependent prion neurotropism.