Concentration and distribution of infectivity and PrP^Sc following partial denaturation of a mouse-adapted and a hamster-adapted scrapie strain

PrP^Sc is a specific protein marker for slow infectious diseases known as the transmissible subacute spongiform encephalopathies. Although PrP^Sc is closely associated with infectivity, it is not known if it is the infectious agent itself, a component of the agent or merely adventitiously associated with infectivity. In the present study we demonstrate that the resistance of PrP^Sc to partial denaturation and of infectivity to inactivation differs markedly for two scrapie strains. Proteinase K treatment or electrophoretic analysis of partially denatured PrP^Sc preparations reveal a dissociation between infectivity and demonstrable PrP^Sc. Our findings support other evidence that not all PrP^Sc is required for infectivity. Our studies combined with previous biological analyses suggest that PrP^Sc cannot be the sole component associated with the infectious agent.