NR AXWV
AU Somerville,R.
TI Diversity in the Biological and Chemical Properties of TSE Agent-Strains: Implications for TSE Agent Structure
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.34
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Under controlled conditions TSE agent strains produce a highly reproducible set of measurable biological properties, notably incubation periods and the distribution and intensity of neuropathological change. These biological properties require TSE infectious agents to be genetically independent of the host, but to replicate under strict host control. Phenotypic properties have been used to characterise a series of experimentally derived TSE strains whose properties can be further compared. Differences in the degree to which PrPsc is glycosylated and its migration on SDSPAGE show phenotypic variation between TSE strains, although these properties are also influenced by host factors.
TSE agents also show strain-specific responses to inactivation with heat, high pH and SDS, suggesting covalent differences in the molecules which comprise the structure of the infective agents. Heat inactivation properties are primarily specified by TSE strain; although passage history in the host can have an effect. Differences in heat inactivation properties have allowed two passage lines of the TSE strain ME7 to be distinguished. The kinetics of the inactivation of TSE agents with heat suggest two different components must be involved in the structure. These findings have not been reconciled with models of TSE agents based solely on the conversion of the host protein PrP into an abnormal conformation that is proposed to be infectious. Much of the abnormal PrPsc can be solubilised into a non-sedimentable form, not associated with TSE infectivity, suggesting that most PrP in the PrPsc fraction is not intrinsically infectious, and that PrP associated with the structure of the infectious agent must form part of a sedimentable particle. Accordingly structural models of TSE agents are being developed to include a mechanism for maintaining and replicating host-independent genetic information and diversity in structure compatible with the differences in inactivation properties between TSE strains.
AD R. Somerville, Roslin Institute Neuropathogenesis Unit, UK
SP englisch
PO Schottland
EA pdf-Datei und Poster (zusätzliche Autorin: K. Fernie, Postertitel: TSE Agent-Strain diversity: implications for TSE agent structure)