Figure 2: Schematic representation of two possible mechanisms of de novo propagation of prions from recPrP fibrils. (a) In this model, the preparation of recPrP fibrils contains very small amounts of classical . A long incubation time is required to amplify and propagate in vivo this minute amount of . (b) The second model (“deformed templating" mechanism) hypothesizes that there is no classical in the fibril preparation and that recPrP fibrils can be converted into PrPres ( -like structures) with low efficiency. After several passages, these -like structures progressively adopt the structural features of classical . Schema adapted from Makarava et al., 2011 [48].