HETEROLOGOUS PRP MOLECULES INTERFERE WITH ACCUMULATION OF PROTEASE-RESISTANT PRP IN SCRAPIE-INFECTED MURINE NEUROBLASTOMA-CELLS

Mutations within a host cellular protein, PrP, have been associated wi th disease in the transmissible spongiform encephalopathies. Murine ne uroblastoma cells persistently infected with mouse scrapie accumulate protease-resistant PrP (PrP-res), the abnormal form of PrP associated with disease in the transmissible spongiform encephalopathies. These c ells provide a controlled system in which to study the molecular inter actions which are important in the formation of PrP-res. We have expre ssed recombinant PrP molecules in mouse scrapie-infected murine neurob lastoma cells and assayed the effect of these heterologous PrP genes o n the formation and accumulation of PrP-res. The results demonstrate t hat expression of heterologous PrP molecules which differ from the end ogenous PrP by as little as one amino acid can profoundly interfere wi th the overall accumulation of PrP-res. The data suggest that precise interactions between homologous PrP molecules are important in PrP-res accumulation and that heterologous PrP molecules can block these inte ractions.