Abstract |
Native mammalian prions exist in self-propagating strains that exhibit distinctive clinical, pathological and biochemical characteristics. Prion strain diversity is associated with variations in PrP(Sc) conformation, but it remains unknown precisely which physical properties of the PrP(Sc) molecules are required to encipher mammalian prion strain phenotypes. In this study, we subjected prion-infected brain homogenates derived from three different hamster scrapie strains to either (i) proteinase K digestion or (ii) sonication, and inoculated the modified samples into normal hamsters. The results show that the strain-specific clinical features and neuropathological profiles of inoculated animals were not affected by either treatment. Similarly, the strain-dependent biochemical characteristics of the PrP(Sc) molecules (including electrophoretic mobility, glycoform composition, conformational stability and susceptibility to protease digestion) in infected animals were unaffected by either proteolysis or sonication of the original inocula. These results indicate that the infectious strain properties of native prions do not appear to be altered by PrP(Sc) disaggregation, and that maintenance of such properties does not require the N-domain (approximately residues 23-90) of the protease-resistant PrP(Sc) molecules or protease-sensitive PrP(Sc) molecules.
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Authors | Andrea M Deleault, Nathan R Deleault, Brent T Harris, Judy R Rees, Surachai Supattapone |
Journal | The Journal of general virology
(J Gen Virol)
Vol. 89
Issue Pt 10
Pg. 2642-2650
(Oct 2008)
ISSN: 0022-1317 [Print] England |
PMID | 18796735
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- PrPSc Proteins
- Prions
- Endopeptidase K
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Topics |
- Animals
- Brain
(metabolism, pathology)
- Cricetinae
- Endopeptidase K
(metabolism)
- Female
- Mesocricetus
- Phenotype
- PrPSc Proteins
(chemistry, classification, metabolism)
- Prions
(chemistry, classification, metabolism)
- Protein Conformation
- Protein Denaturation
- Scrapie
(metabolism, pathology, transmission)
- Sonication
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