Comparative studies on the thermostability of five strains of transmissible-spongiform-encephalopathy agent

The causal infectious agents of TSEs (transmissible spongiform encephalopathies or prion diseases) are renowned for their resistance to complete inactivation. Survival of TSE infectivity after autoclaving potentially compromises many procedures where TSE infectivity may be present, including surgical instrument sterilization. In the present study, the heat inactivation properties of five different TSE agents were tested in a variety of experiments by exposing them to a range of heat inactivation conditions. Although TSE infectivity was reduced after heating to 200 degrees C in a hot air oven, substantial amounts of infectivity remained. Unlike wet heat inactivation, no TSE strain-dependent differences were observed in the reduction in the amounts of infectivity produced by dry heat inactivation. However, the incubation periods of mice infected with one dry heated TSE strain, ME7, were substantially prolonged, whereas there was little or no effect for two other TSE models. Varying autoclaving conditions for three TSE strains between 132 and 138 degrees C, and times of exposure between 30 and 120 min, had little or no effect on the recovery of TSE infectivity. The results illustrate the limitations of TSE agent inactivation using heat-based methods. The results support the hypothesis that the structures of TSE agents are stabilized during heat-inactivation procedures, rendering them much more refractory to inactivation. This may occur through dehydration of the causal agents, specifically through the removal of the water of solvation from agent structures and hence stabilize interactions between prion protein and TSE agent-specific ligands.