REVERSIBILITY OF SCRAPIE INACTIVATION IS ENHANCED BY COPPER

The only known difference between the cellular (PrPC) and scrapie-spec ific (PrPSc) isoforms of the prion protein is conformational. Because disruption of PrPSc structure decreases scrapie infectivity, restorati on of the disease-specific conformation should restore infectivity. In this study, disruption of PrPSc (as monitored by the loss of proteina se K resistance) by guanidine hydrochloride (GdnHCl) resulted in decre ased infectivity. Upon dilution of the GdnHCl, protease resistance of PrP was restored and infectivity was regained. The addition of copper facilitated restoration of both infectivity and protease resistance of PrP in a subset of samples that did not renature by the simple diluti on of the GdnHCl, These data demonstrate that loss of scrapie infectiv ity can be a reversible process and that copper can enhance this resto ration of proteinase K resistance and infectivity.