Resistance of scrapie infectivity to steam autoclaving after formaldehyde fixation and limited survival after ashing at 360 degrees C: practical and theoretical implications.

Scrapie-infected hamster brains and their extracted amyloid fibrils were subjected to formaldehyde and steam autoclaving, alone or in combination. Treatment with formaldehyde before autoclaving stabilized infectivity, whereas treatment after autoclaving was either inactive or further reduced infectivity. In additional experiments on specimens (not treated with formaldehyde) that were subjected to dry heat, a small amount of infectivity still survived a 1-h exposure to temperatures as high as 360 degrees C. These results are consistent with the operation of a comparatively primitive molecular mechanism for the initiation of scrapie agent replication (perhaps an inorganic crystal nucleation step) and the subsequent participation of an organic macromolecule (scrapie amyloid protein) that is susceptible to intramolecular cross-stabilization by formaldehyde.