Results: We have established a system in dissociated cell culture in which scrapie-infected mouse SMB cells are able to stably convert genetically marked target cells by coculture. After coculture and rigorous removal of SMB cells, the target cells express PrPSc and also incorporate [S-35]methionine into PrPSc. The extent of conversion was sensitive to the ratio of the two cell types, and conversion by live SMB required 2500-fold less PrPSc than conversion by a cell-free prion preparation. The conversion activity of SMB cells is not detectable in conditioned medium and apparently depends on close proximity or contact, as evidenced by culturing the SMB and target cells on neighboring but separate surfaces. SMB cells were killed by fixation in aldehydes, followed by washing, and were found to retain significant activity at conversion of target cells.

Conclusions: Cell-mediated infection of target cells in this culture system is effective and requires significantly less PrPSc than infection by a prion preparation. Several lines of evidence indicate that it depends on cell contact, in particular, the activity of aldehyde-fixed infected cells.