title: The effects of prion protein proteolysis and disaggregation on the strain properties of hamster scrapie.
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.
authors.affiliation: Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Deleault
authors.affiliation: Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Deleault
authors.affiliation: Department of Pathology, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Brent T
authors.initials: BT
authors.lastname: Harris
authors.affiliation: Department of Community and Family Medicine (Biostatistics and Epidemiology), Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Judy R
authors.initials: JR
authors.lastname: Rees
authors.affiliation: Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA.|Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Surachai
authors.initials: S
authors.lastname: Supattapone
mesh_terms: 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
chemical_list: D018620:PrPSc Proteins; D011328:Prions; D019286:Endopeptidase K
references.citation: J Biol Chem. 1988 Apr 5;263(10):4950-5
references.pmid: 3350818
references.citation: Cell. 1983 Dec;35(2 Pt 1):349-58
references.pmid: 6418385
references.citation: Nature. 1969 May 31;222(5196):892-3
references.pmid: 4976976
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2042-7
references.pmid: 10051591
references.citation: Nat Rev Microbiol. 2007 Aug;5(8):611-8
references.pmid: 17632572
references.citation: Protein Sci. 2001 Apr;10(4):854-63
references.pmid: 11274476
references.citation: Science. 2005 Oct 14;310(5746):324-6
references.pmid: 16224026
references.citation: Science. 2006 Oct 6;314(5796):133-6
references.pmid: 17023660
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9741-6
references.pmid: 17535913
references.citation: Biochemistry. 1989 Oct 17;28(21):8380-8
references.pmid: 2574992
references.citation: Curr Top Microbiol Immunol. 1996;207:35-47
references.pmid: 8575205
references.citation: J Virol. 2006 Jan;80(1):322-31
references.pmid: 16352557
references.citation: J Gen Virol. 1996 Apr;77 ( Pt 4):811-3
references.pmid: 8627270
references.citation: Cell. 2005 Apr 22;121(2):195-206
references.pmid: 15851027
references.citation: J Virol. 2001 Feb;75(3):1408-13
references.pmid: 11152514
references.citation: Science. 1996 Dec 20;274(5295):2079-82
references.pmid: 8953038
references.citation: J Gen Virol. 1983 Sep;64 (Pt 9):2045-50
references.pmid: 6411862
references.citation: Eur J Biochem. 1988 Sep 1;176(1):21-30
references.pmid: 3138115
references.citation: J Virol. 1992 Apr;66(4):2096-101
references.pmid: 1347795
references.citation: J Biol Chem. 2007 Dec 7;282(49):35878-86
references.pmid: 17923484
references.citation: Cell. 1984 Aug;38(1):127-34
references.pmid: 6432339
references.citation: Br Med Bull. 1993 Oct;49(4):822-38
references.pmid: 8137131
references.citation: Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8531-5
references.pmid: 11438695
references.citation: Proc Natl Acad Sci U S A. 1986 Sep;83(17):6372-6
references.pmid: 3462700
references.citation: Biochemistry. 2006 Dec 26;45(51):15710-7
references.pmid: 17176093
references.citation: Nature. 1967 Dec 30;216(5122):1310-1
references.pmid: 5625087
references.citation: Biochemistry. 2003 Jun 10;42(22):6794-803
references.pmid: 12779334
references.citation: Nat Med. 1998 Oct;4(10):1157-65
references.pmid: 9771749
references.citation: J Mol Biol. 2005 Mar 11;346(5):1393-407
references.pmid: 15713489
references.citation: Biochem J. 2007 Feb 15;402(1):17-23
references.pmid: 17155929
references.citation: J Biol Chem. 2002 May 24;277(21):18421-30
references.pmid: 11882649
references.citation: Cell. 1987 Oct 23;51(2):229-40
references.pmid: 2444340
references.citation: Bioprocess Technol. 1991;12:57-83
references.pmid: 1367090
references.citation: Arch Neurol. 2005 Apr;62(4):545-52
references.pmid: 15824251
references.citation: J Virol. 1994 Dec;68(12):7859-68
references.pmid: 7966576
references.citation: Lancet. 2000 Nov 18;356(9243):1772
references.pmid: 11095289
references.citation: Nature. 1996 Oct 24;383(6602):685-90
references.pmid: 8878476
references.citation: EMBO J. 2001 Sep 17;20(18):5070-8
references.pmid: 11566872
references.citation: Lancet. 1991 Feb 2;337(8736):269-70
references.pmid: 1671114
references.citation: J Virol. 2000 May;74(9):4351-60
references.pmid: 10756050
references.citation: Science. 1982 Apr 9;216(4542):136-44
references.pmid: 6801762
references.citation: Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6449-53
references.pmid: 8101989
references.citation: Nat Med. 2005 Nov;11(11):1137-8
references.pmid: 16270061