The endogenous protease-sensitive prion protein (PrP-sen) of the host is changed to an aberrant pathogenic version with a characteristic partial protease resistance in transmissible spongiform encephalopathies (TSE) or prion disorders (PrP-res). PrP-res can directly trigger this conversion of PrP-sen, according to studies with cellfree reactions. This PrPres-induced conversion reaction is highly specific in ways that could account for TSE species barriers, polymorphism barriers, and strains at the molecular level. This reaction has been detected in TSEinfected brain slices as well as in mainly pure PrP-sen and PrP-res reactants. The binding of PrP-sen to polymeric PrP-res and a conformational shift that results in incorporation into the PrP-res polymer appear to be involved in the conversion pathway.
