1887

Abstract

The causal agents of the transmissible spongiform encephalopathy (TSE) diseases, sometimes called prion diseases, are characterized by high resistance to inactivation with heat. Results from thermal inactivation experiments on nine TSE strains, seven passaged in two PrP genotypes, showed differences in sensitivity to heat inactivation ranging over 17 °C. In addition, the rate of inactivation with increasing temperature varied between TSE models. In some cases passage in an alternative PrP genotype had little effect on the resulting inactivation properties, but for others the infectious agent was inactivated at lower temperatures. No strain with higher thermostability properties was selected. The effect of mixing two TSE strains, to see whether their properties were affected through interaction with each other, was also examined. The results showed that both strains behaved as expected from the behaviour of the unmixed controls, and that the strain responsible for inducing TSE disease could be identified. There was no evidence of a direct effect on intrinsic strain properties. Overall, the results illustrate the diversity in properties of TSE strains. They require intrinsic molecular properties of TSE agents to accommodate high resistance to inactivation and a mechanism, independent of the host, to directly encode these differences. These findings are more readily reconciled with models of TSE agents with two separate components, one of which is independent of the host and comprises a TSE-specific nucleic acid, than with models based solely on conformational changes to a host protein.

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2011-07-01
2019-10-21
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vol. , part 7, pp. 1738–1748

Primary incubation period data. Pairwise comparisons of values of . Pairwise comparisons of values of . Calculating titres from incubation periods. Lesion profiles from experiments using ME7 and 87A. Lesion profiles from experiments using of 22C, 22A and 22F. Lesion profiles from experiments using of 79A (a and b) and 139A (c and d). Lesion profiles from experiments using 301C (a, b and c) and 301V (d and e). Lesion profiles from experiments using mixtures of ME7 and 301V.

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