Alteration of cell responses to PrP(Sc) in prolonged cell culture and its effect on transmission of PrP(Sc) to neural cells.

The mechanisms and processes of the uptake, intracellular trafficking and intercellular spread of PrP(Sc) and its transfer to neural cells are not clearly defined. The involvement of immune, intestinal, mast or peripheral neural cells in this process also remains unclear. The role of these cell types in the accumulation and transfer of PrP(Sc) to neural cells was investigated following short and prolonged exposure to the Chandler and Obihiro strains of scrapie PrP(Sc) for up to 28 days. Eight cell lines of murine immune, neural, intestinal and fibroblast cell types were tested. After transient degradation phases, certain immune, intestinal and neural cells accumulated PrP(Sc) for up to 28 days postinfection. When co-cultured with N2a-3/EGFP neuroblastoma cells for 4 days followed by several passages, the immune, intestinal and the neural cell lines were able to transfer infection to neural cells. Our results suggest that some of these cell types may have a role in PrP(Sc) accumulation and intercellular spread of PrP(Sc) infection to neural cells in vivo.