title: Characterization of thermodynamic diversity between transmissible spongiform encephalopathy agent strains and its theoretical implications.
abstract: Some transmissible spongiform encephalopathy (TSE) (or "prion") strains, notably those derived from bovine spongiform encephalopathy, are highly resistant to total inactivation by heat. When three TSE strains derived from sheep with scrapie were heated, little inactivation took place at low temperatures, but at higher temperatures, considerable inactivation occurred. The temperature at which substantial inactivation first occurred varied according to TSE strain, and it was calculated to be 70 degrees C for the 22C strain, 84 degrees C for ME7, and 97 degrees C for 22A by fitting the data to a model based on competition between a destructive and a protective reaction. However, PrP(Sc) from mice infected with a range of TSE strains retained similar resistance to proteinase K digestion after heating to below or above these temperatures, showing that the properties of PrP(Sc) responsible for proteinase resistance do not correlate with those conferring thermostability on the TSE agent. The simplest explanation of these data is that the causal agent contains a macromolecular component that is structurally independent of the host, that it varies covalently between TSE strains, and that it is protected by other macromolecular components. The model is in accord with the virino hypothesis, which proposes a host-independent informational molecule protected by the host protein PrP.
authors.affiliation: Neuropathogenesis Unit, Institute for Animal Health, West Mains Road, Edinburgh EH9 3JF, United Kingdom. robert.somerville@bbsrc.ac.uk
authors.forename: Robert A
authors.initials: RA
authors.lastname: Somerville
authors.forename: Radulf C
authors.initials: RC
authors.lastname: Oberthur
authors.forename: Ulrich
authors.initials: U
authors.lastname: Havekost
authors.forename: Fiona
authors.initials: F
authors.lastname: MacDonald
authors.forename: David M
authors.initials: DM
authors.lastname: Taylor
authors.forename: Alan G
authors.initials: AG
authors.lastname: Dickinson
mesh_terms: D006358:Hot Temperature; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011328:Prions