NR AWOB
AU Somerville,R.A.; Gentles,N.; Fernie,K.
TI Characterization of the effect of heat on TSE agent-strains
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions S-24
PT Konferenz-Poster
AB We are developing models of TSE inactivation processes, focusing particularly on heat inactivation. The degree of diversity in thermostability of TSE agent strains has been investigated in 9 TSE strains, seven of which were passaged in two PrP genotypes to give a total 16 TSE models. They show a wide diversity of properties, with differences in heat inactivation of more than 20 deg C. In addition, the rate of inactivation from different TSE models with increasing temperature varied between TSE models. In some cases passage in the alternate PrP genotype had little effect on the resulting inactivation properties but in three cases inactivation occurred at lower temperatures. Mixing two TSE strains showed that both strains behaved as expected from the behaviour of the unmixed control, and that the strain causing TSE disease could be identified. There was no evidence of a direct effect of heating on intrinsic strain properties. No strain with higher thermostability properties was selected, either directly after heating or after passage in an alternate PrP genotype. However TSE models with lower thermostability were observed after passage in alternate PrP genotypes. Physical or chemical treatments of TSE agents prior to heating could in some cases alter thermostability properties. Thermostability did not correlate with pH stability. However biochemical analysis of PrPsc in the TSE models under investigation showed an apparent correlation between the degree to which PrPsc was glycosylated and the resistance to heat inactivation of the TSE model. The results illustrate in a novel way the diversity of TSE strains. They require molecular properties of TSE agents to accommodate high resistance to inactivation; and a mechanism, independent of the host, which encodes these differences. It is hard to imagine how a host protein might accommodate these requirements by itself.
AD Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh, EH9 3JF, UK. E-mail: robert.somerville@bbsrc.ac.uk
SP englisch
PO Italien