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
2024-04-19
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References

  1. Angers R. C., Kang H. E., Napier D., Browning S., Seward T., Mathiason C., Balachandran A., McKenzie D., Castilla J. et al. 2010; Prion strain mutation determined by prion protein conformational compatibility and primary structure. Science 328:1154–1158 [View Article][PubMed]
    [Google Scholar]
  2. Baskakov I. V. 2009; Switching in amyloid structure within individual fibrils: implication for strain adaptation, species barrier and strain classification. FEBS Lett 583:2618–2622 [View Article][PubMed]
    [Google Scholar]
  3. Brown P., Liberski P. P., Wolff A., Gajdusek D. C. 1990; Resistance of scrapie infectivity to steam autoclaving after formaldehyde fixation and limited survival after ashing at 360 °C: practical and theoretical implications. J Infect Dis 161:467–472 [View Article][PubMed]
    [Google Scholar]
  4. Bruce M. E., Dickinson A. G. 1987; Biological evidence that scrapie agent has an independent genome. J Gen Virol 68:79–89 [View Article][PubMed]
    [Google Scholar]
  5. Bruce M. E., McConnell I., Fraser H., Dickinson A. G. 1991; The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis. J Gen Virol 72:595–603 [View Article][PubMed]
    [Google Scholar]
  6. Bruce M., Chree A., McConnell I., Foster J., Pearson G., Fraser H. 1994; Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier. Philos Trans R Soc Lond B Biol Sci 343:405–411 [View Article][PubMed]
    [Google Scholar]
  7. Carp R. I., Meeker H., Sersen E. 1997; Scrapie strains retain their distinctive characteristics following passages of homogenates from different brain regions and spleen. J Gen Virol 78:283–290[PubMed]
    [Google Scholar]
  8. Caughey B., Raymond G. J., Bessen R. A. 1998; Strain-dependent differences in β-sheet conformations of abnormal prion protein. J Biol Chem 273:32230–32235 [View Article][PubMed]
    [Google Scholar]
  9. Deleault N. R., Harris B. T., Rees J. R., Supattapone S. 2007; Formation of native prions from minimal components in vitro . Proc Natl Acad Sci U S A 104:9741–9746 [View Article][PubMed]
    [Google Scholar]
  10. Dickinson A. G. 1976; Scrapie in sheep and goats. Front Biol 44:209–241[PubMed]
    [Google Scholar]
  11. Dickinson A. G., Fraser H. 1969; Modification of the pathogenesis of scrapie in mice by treatment of the agent. Nature 222:892–893 [View Article][PubMed]
    [Google Scholar]
  12. Dickinson A. G., Taylor D. M. 1978; Resistance of scrapie agent to decontamination. N Engl J Med 299:1413–1414 [View Article][PubMed]
    [Google Scholar]
  13. Dickinson A. G., Meikle V. M., Fraser H. 1968; Identification of a gene which controls the incubation period of some strains of scrapie agent in mice. J Comp Pathol 78:293–299 [View Article][PubMed]
    [Google Scholar]
  14. Dickinson A. G., Fraser H., Meikle V. M., Outram G. W. 1972; Competition between different scrapie agents in mice. Nat New Biol 237:244–245[PubMed] [CrossRef]
    [Google Scholar]
  15. Domingo E., Menéndez-Arias L., Holland J. J. 1997; RNA virus fitness. Rev Med Virol 7:87–96 [View Article][PubMed]
    [Google Scholar]
  16. Farquhar C. F., Somerville R. A., Bruce M. E. 1998; Straining the prion hypothesis. Nature 391:345–346 [View Article][PubMed]
    [Google Scholar]
  17. Fernie K., Steele P. J., Taylor D. M., Somerville R. A. 2007; Comparative studies on the thermostability of five strains of transmissible-spongiform-encephalopathy agent. Biotechnol Appl Biochem 47:175–183 [View Article][PubMed]
    [Google Scholar]
  18. Fraser H., Dickinson A. G. 1967; Distribution of experimentally induced scrapie lesions in the brain. Nature 216:1310–1311 [View Article][PubMed]
    [Google Scholar]
  19. Kimberlin R. H., Walker C. A., Millson G. C., Taylor D. M., Robertson P. A., Tomlinson A. H., Dickinson A. G. 1983; Disinfection studies with two strains of mouse-passaged scrapie agent. Guidelines for Creutzfeldt–Jakob and related agents. J Neurol Sci 59:355–369 [View Article][PubMed]
    [Google Scholar]
  20. Kimberlin R. H., Walker C. A., Fraser H. 1989; The genomic identity of different strains of mouse scrapie is expressed in hamsters and preserved on reisolation in mice. J Gen Virol 70:2017–2025 [View Article][PubMed]
    [Google Scholar]
  21. Li J., Browning S., Mahal S. P., Oelschlegel A. M., Weissmann C. 2010; Darwinian evolution of prions in cell culture. Science 327:869–872 [View Article][PubMed]
    [Google Scholar]
  22. Makarava N., Kovacs G. G., Bocharova O., Savtchenko R., Alexeeva I., Budka H., Rohwer R. G., Baskakov I. V. 2010; Recombinant prion protein induces a new transmissible prion disease in wild-type animals. Acta Neuropathol 119:177–187 [View Article][PubMed]
    [Google Scholar]
  23. Manuelidis L. 2010; Nuclease resistant circular DNAs copurify with infectivity in scrapie and CJD. J Neurovirol 17:131–145 [View Article][PubMed]
    [Google Scholar]
  24. Matousek J., Orctová L., Steger G., Skopek J., Moors M., Dedic P., Riesner D. 2004; Analysis of thermal stress-mediated PSTVd variation and biolistic inoculation of progeny of viroid “thermomutants” to tomato and Brassica species. Virology 323:9–23 [View Article][PubMed]
    [Google Scholar]
  25. Nishida N., Katamine S., Manuelidis L. 2005; Reciprocal interference between specific CJD and scrapie agents in neural cell cultures. Science 310:493–496 [View Article][PubMed]
    [Google Scholar]
  26. Peleg M. 1996; Evaluation of the Fermi equation as a model of dose response curves. Appl Microbiol Biotechnol 46:303–306 [View Article]
    [Google Scholar]
  27. Rohwer R. G. 1984; Virus like sensitivity of the scrapie agent to heat inactivation. Science 223:600–602 [View Article][PubMed]
    [Google Scholar]
  28. Simoneau S., Ruchoux M., Vignier N., Lebon P., Freire S., Comoy E., Deslys J., Fournier J. 2009; Small critical RNAs in the scrapie agent. Nature Precedings hdl:10101/npre.2009.3344.1
    [Google Scholar]
  29. Somerville R. A. 2002; TSE agent strains and PrP: reconciling structure and function. Trends Biochem Sci 27:606–612 [View Article][PubMed]
    [Google Scholar]
  30. Somerville R. A., Oberthür R. C., Havekost U., MacDonald F., Taylor D. M., Dickinson A. G. 2002; Characterization of thermodynamic diversity between transmissible spongiform encephalopathy agent strains and its theoretical implications. J Biol Chem 277:11084–11089 [View Article][PubMed]
    [Google Scholar]
  31. Somerville R. A., Hamilton S., Fernie K. 2005; Transmissible spongiform encephalopathy strain, PrP genotype and brain region all affect the degree of glycosylation of PrPSc. . J Gen Virol 86:241–246 [View Article][PubMed]
    [Google Scholar]
  32. Taylor D. 2000; Inactivation of transmissible degenerative encephalopathy agents: a review. Veterinary Journal 159:10–7 [View Article][PubMed]
    [Google Scholar]
  33. Taylor D. M., Fernie K. 1996; Exposure to autoclaving or sodium hydroxide extends the dose–response curve of the 263K strain of scrapie agent in hamsters. J Gen Virol 77:811–813 [View Article][PubMed]
    [Google Scholar]
  34. Taylor D. M., Fraser H., McConnell I., Brown D. A., Brown K. L., Lamza K. A., Smith G. R. A. 1994; Decontamination studies with the agents of bovine spongiform encephalopathy and scrapie. Arch Virol 139:313–326 [View Article][PubMed]
    [Google Scholar]
  35. Taylor D. M., Woodgate S. L., Atkinson M. J. 1995; Inactivation of the bovine spongiform encephalopathy agent by rendering procedures. Vet Rec 137:605–610[PubMed]
    [Google Scholar]
  36. Taylor D. M., McConnell I., Fernie K. 1996; The effect of dry heat on the ME7 strain of mouse-passaged scrapie agent. J Gen Virol 77:3161–3164 [View Article][PubMed]
    [Google Scholar]
  37. Taylor D. M., Woodgate S. L., Fleetwood A. J., Cawthorne R. J. 1997; Effect of rendering procedures on the scrapie agent. Vet Rec 141:643–649[PubMed] [CrossRef]
    [Google Scholar]
  38. Taylor D. M., Fernie K., McConnell I., Steele P. J. 1998; Observations on thermostable subpopulations of the unconventional agents that cause transmissible degenerative encephalopathies. Vet Microbiol 64:33–38 [View Article][PubMed]
    [Google Scholar]
  39. Taylor D. M., Fernie K., Steele P. J., McConnell I., Somerville R. A. 2002; Thermostability of mouse-passaged BSE and scrapie is independent of host PrP genotype: implications for the nature of the causal agents. J Gen Virol 83:3199–3204[PubMed]
    [Google Scholar]
  40. Thomzig A., Spassov S., Friedrich M., Naumann D., Beekes M. 2004; Discriminating scrapie and bovine spongiform encephalopathy isolates by infrared spectroscopy of pathological prion protein. J Biol Chem 279:33847–33854 [View Article][PubMed]
    [Google Scholar]
  41. Vignuzzi M., Stone J. K., Arnold J. J., Cameron C. E., Andino R. 2006; Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature 439:344–348 [View Article][PubMed]
    [Google Scholar]
  42. Walker A. S., Inderlied C. B., Kingsbury D. T. 1983; Conditions for the chemical and physical inactivation of the K. Fu. strain of the agent of Creutzfeldt–Jakob disease. Am J Public Health 73:661–665 [View Article][PubMed]
    [Google Scholar]
  43. Wang F., Wang X., Yuan C. G., Ma J. 2010; Generating a prion with bacterially expressed recombinant prion protein. Science 327:1132–1135 [CrossRef]
    [Google Scholar]
  44. Wilesmith J. W., Wells G. A., Cranwell M. P., Ryan J. B. 1988; Bovine spongiform encephalopathy: epidemiological studies. Vet Rec 123:638–644[PubMed]
    [Google Scholar]
  45. Wilesmith J. W., Ryan J. B., Atkinson M. J. 1991; Bovine spongiform encephalopathy: epidemiological studies on the origin. Vet Rec 128:199–203 [View Article][PubMed]
    [Google Scholar]
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