The effects of prion protein proteolysis and disaggregation on the strain properties of hamster scrapie.
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.
Deleault
Andrea M
AM
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.
Deleault
Nathan R
NR
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.
Harris
Brent T
BT
Department of Pathology, Dartmouth Medical School, Hanover, NH 03755, USA.
Rees
Judy R
JR
Department of Community and Family Medicine (Biostatistics and Epidemiology), Dartmouth Medical School, Hanover, NH 03755, USA.
Supattapone
Surachai
S
Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA.|Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D019286:Endopeptidase K / Q000378:metabolism*; D005260:Female; D008647:Mesocricetus; D010641:Phenotype; D018620:PrPSc Proteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D011487:Protein Conformation; D011489:Protein Denaturation; D012608:Scrapie / Q000378:metabolism / Q000473:pathology / Q000635:transmission; D013010:Sonication
D018620:PrPSc Proteins; D011328:Prions; D019286:Endopeptidase K
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