Prions Ex Vivo: What Cell Culture Models Tell Us about Infectious Proteins
Figure 1
Induction of a PrP or Sup35 NM prion phenotype in mammalian cells. (a) Mammalian prions can infect selected cell cultures. Exposure of permissive cells to brain homogenate containing PrPSc leads to infection of cells. Prions persist mainly through stable inheritance of PrPSc aggregates by daughter cells. Prions also spread to adjacent cells by cell-to-cell contact or exosomes and induce productive infection in recipient cells. (b) Artificial prions produced in vitro from recombinant prion proteins. PrP aggregates derived from PrP and minimal components by PMCA are infectious to some cell lines. The increase in PrPSc over time suggests that prions propagate, likely by vertical transmission to daughter cells. Spreading to adjacent cells has not been studied so far. (c) Recombinant NM fibrils produce a heritable NM aggregation phenotype in N2a cells expressing a GPI-anchored NM-GFP fusion protein. When N2a cells that spontaneously form mCherry-tagged NM-GPI aggregates are cocultured with NM-GFP-GPI expressing cells, they induce NM aggregation in neighboring cells. (d) Cytosolically expressed NM-HA is soluble but can be induced to aggregate upon addition of recombinant NM fibrils. The NM aggregate phenotype is transmitted vertically and horizontally.
