Scrapie prion protein accumulation by scrapie-infected neuroblastoma cellsabrogated by exposure to a prion protein antibody

Exposure of susceptible neuroblastoma N2a cells to mouse scrapie prions lea ds to infection, as evidenced by the continued presence of the scrapie form of the prion protein (PrPSc) and infectivity after 300 or more cell doubli ngs. We find that exposure to phosphatidylinositol-specific phospholipase C (PIPLC) or to the monoclonal anti-prion protein (PrP) antibody 6H4 not onl y prevents infection of susceptible N2a cells but also cures chronically sc rapie-infected cultures, as judged by the long-term abrogation of PrPSc acc umulation after cessation of treatment. A nonpassaged, stationary infected culture rapidly loses PrPSc when exposed to the antibody or PIPLC, indicati ng that the PrPSc level is determined by steady state equilibrium between f ormation and degradation, and that depletion of the cellular form of PrP ca n interrupt the propagation of PrPSc. These findings encourage the belief t hat passive immunization may provide a therapeutic approach to prion diseas e.