NR AOZH
AU Somerville,R.A.; Fernie,K.; Steele,P.J.; Hamilton,S.; Gentles,N.
TI Do the properties of TSE agents and PrPsc differ?
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-121
PT Konferenz-Poster
AB The amount of PrPsc in many TSE models exceeds that of the infective agent. Although TSE infectivity and PrPsc tend to co-purify, the relationship between them is not clear and some PrPsc can be separated from infectious fractions. These and other findings raise questions about the relationship between the TSE agent and PrPsc. We have been comparing the effects of physical and chemical treatments on both PrPsc and a panel of TSE strains. TSE agent strains are inactivated biphasically with respect to time and temperature. They show different degrees of thermostability with respect to strain whereas the properties of PrPsc are similar from a range of TSE strains. Combining treatments at a range of temperatures from 20 C to 100 C and pH from pH 7.4 to pH 12 suggests that these two factors operate synergistically to inactivate TSE infectivity. These data suggest that TSE agents are comprised of two components whose interactions are disrupted by high pH and temperature combinations in a TSE strain-specific fashion. A combination of high pH and temperature resulted in the loss of resistance of PrPsc to proteinase K digestion. At higher pH values PrP is destroyed. In both cases PrP is lost with exponential decay kinetics. Treatment with Guanidine HCl resulted in monophasic kinetics of TSE inactivation with respect to increasing concentration of Guanidine and temperature below temperatures which inactivate TSE infectivity in aqueous solution. No differences between TSE strains have been observed. The heat inactivation data fit a two component model of TSE agents. However protein is denatured by chaotropes independently of other components. The survival properties of PrPsc and the kinetics of its change in properties or its loss appear to differ from those of TSE agent strains. These data fit with a model of TSE agents in which a molecule carrying host-independent genetic information is protected by protein, probably PrP.
AD Robert A. Somerville, Karen Fernie, Philip J. Steele, Scott Hamilton, Nicola Gentles, Neuropathogenesis Unit, UK
SP englisch
PO Deutschland