{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T01:13:07Z","timestamp":1769389987751,"version":"3.49.0"},"reference-count":37,"publisher":"Microbiology Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,8,1]]},"abstract":"<jats:p>Distinct prion strains can be distinguished by differences in incubation period, neuropathology and biochemical properties of disease-associated prion protein (PrP<jats:sup>Sc<\/jats:sup>) in inoculated mice. Reliable comparisons of mouse prion strain properties can only be achieved after passage in genetically identical mice, as host prion protein sequence and genetic background are known to modulate prion disease phenotypes. While multiple prion strains have been identified in sheep scrapie and Creutzfeldt\u2013Jakob disease, bovine spongiform encephalopathy (BSE) is thought to be caused by a single prion strain. Primary passage of BSE prions to different lines of inbred mice resulted in the propagation of two distinct PrP<jats:sup>Sc<\/jats:sup> types, suggesting that two prion strains may have been isolated. To investigate this further, these isolates were subpassaged in a single line of inbred mice (SJL) and it was confirmed that two distinct prion strains had been identified. MRC1 was characterized by a short incubation time (110\u00b13\u2005days), a mono-glycosylated-dominant PrP<jats:sup>Sc<\/jats:sup> type and a generalized diffuse pattern of PrP-immunoreactive deposits, while MRC2 displayed a much longer incubation time (155\u00b11\u2005days), a di-glycosylated-dominant PrP<jats:sup>Sc<\/jats:sup> type and a distinct pattern of PrP-immunoreactive deposits and neuronal loss. These data indicate a crucial involvement of the host genome in modulating prion strain selection and propagation in mice. It is possible that multiple disease phenotypes may also be possible in BSE prion infection in humans and other animals.<\/jats:p>","DOI":"10.1099\/vir.0.79889-0","type":"journal-article","created":{"date-parts":[[2004,7,21]],"date-time":"2004-07-21T21:20:07Z","timestamp":1090444807000},"page":"2471-2478","source":"Crossref","is-referenced-by-count":42,"title":["Characterization of two distinct prion strains derived from bovine spongiform encephalopathy transmissions to inbred mice"],"prefix":"10.1099","volume":"85","author":[{"given":"Sarah E.","family":"Lloyd","sequence":"first","affiliation":[{"name":"MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline M.","family":"Linehan","sequence":"additional","affiliation":[{"name":"MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Desbruslais","sequence":"additional","affiliation":[{"name":"MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Joiner","sequence":"additional","affiliation":[{"name":"MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Buckell","sequence":"additional","affiliation":[{"name":"MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Brandner","sequence":"additional","affiliation":[{"name":"MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan D. F.","family":"Wadsworth","sequence":"additional","affiliation":[{"name":"MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[{"name":"MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"6358","DOI":"10.1093\/emboj\/cdf653","article-title":"BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein","volume":"21","author":"Asante","year":"2002","journal-title":"EMBO J"},{"key":"R2","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1128\/JVI.66.4.2096-2101.1992","article-title":"Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent","volume":"66","author":"Bessen","year":"1992","journal-title":"J Virol"},{"key":"R3","doi-asserted-by":"crossref","first-page":"7859","DOI":"10.1128\/JVI.68.12.7859-7868.1994","article-title":"Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy","volume":"68","author":"Bessen","year":"1994","journal-title":"J Virol"},{"key":"R4","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/sj.embor.7400054","article-title":"Distinct molecular phenotypes in bovine prion diseases","volume":"5","author":"Biacabe","year":"2004","journal-title":"EMBO Rep"},{"key":"R5","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1093\/oxfordjournals.bmb.a072649","article-title":"Scrapie strain variation and mutation","volume":"49","author":"Bruce","year":"1993","journal-title":"Br Med Bull"},{"key":"R6","first-page":"497","article-title":"The basis of strain variation in scrapie","volume-title":"In Prion Diseases of Human and Animals","author":"Bruce","year":"1992"},{"key":"R7","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1098\/rstb.1994.0036","article-title":"Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier","volume":"343","author":"Bruce","year":"1994","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"R8","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/39057","article-title":"Transmissions to mice indicate that \u2018new variant\u2019 CJD is caused by the BSE agent","volume":"389","author":"Bruce","year":"1997","journal-title":"Nature"},{"key":"R9","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1099\/0022-1317-83-3-695","article-title":"Strain characterization of natural sheep scrapie and comparison with BSE","volume":"83","author":"Bruce","year":"2002","journal-title":"J Gen Virol"},{"key":"R10","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/0092-8674(86)90875-5","article-title":"Linkage of prion protein and scrapie incubation time genes","volume":"46","author":"Carlson","year":"1986","journal-title":"Cell"},{"key":"R11","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1073\/pnas.0305777101","article-title":"Identification of a second bovine amyloidotic spongiform encephalopathy: molecular similarities with sporadic Creutzfeldt\u2013Jakob disease","volume":"101","author":"Casalone","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R12","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0140-6736(99)05128-4","article-title":"Variant Creutzfeldt\u2013Jakob disease","volume":"354","author":"Collinge","year":"1999","journal-title":"Lancet"},{"key":"R13","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/378779a0","article-title":"Unaltered susceptibility to BSE in transgenic mice expressing human prion protein","volume":"378","author":"Collinge","year":"1995","journal-title":"Nature"},{"key":"R14","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/383685a0","article-title":"Molecular analysis of prion strain variation and the aetiology of \u2018new variant\u2019 CJD","volume":"383","author":"Collinge","year":"1996","journal-title":"Nature"},{"key":"R15","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1136\/vr.134.17.449","article-title":"Transmission of feline spongiform encephalopathy to mice","volume":"134","author":"Fraser","year":"1994","journal-title":"Vet Rec"},{"key":"R16","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/2151043a0","article-title":"Self replication and scrapie","volume":"215","author":"Griffith","year":"1967","journal-title":"Nature"},{"key":"R17","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/38925","article-title":"The same prion strain causes vCJD and BSE","volume":"389","author":"Hill","year":"1997","journal-title":"Nature"},{"key":"R18","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0304-3940(98)00736-8","article-title":"Molecular screening of sheep for bovine spongiform encephalopathy","volume":"255","author":"Hill","year":"1998","journal-title":"Neurosci Lett"},{"key":"R19","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1093\/brain\/awg125","article-title":"Molecular classification of sporadic Creutzfeldt\u2013Jakob disease","volume":"126","author":"Hill","year":"2003","journal-title":"Brain"},{"key":"R20","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/BF03402129","article-title":"Differences in proteinase K resistance and neuronal deposition of abnormal prion proteins characterize bovine spongiform encephalopathy (BSE) and scrapie strains","volume":"5","author":"Kuczius","year":"1999","journal-title":"Mol Med"},{"key":"R21","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/381743a0","article-title":"BSE transmission to macaques","volume":"381","author":"Lasmezas","year":"1996","journal-title":"Nature"},{"key":"R22","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.1073\/pnas.041490898","article-title":"Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt\u2013Jakob disease: implications for human health","volume":"98","author":"Lasmezas","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R23","doi-asserted-by":"crossref","first-page":"6279","DOI":"10.1073\/pnas.101130398","article-title":"Identification of multiple quantitative trait loci linked to prion disease incubation period in mice","volume":"98","author":"Lloyd","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R24","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s10048-002-0133-9","article-title":"Identification of genetic loci affecting mouse-adapted bovine spongiform encephalopathy incubation time in mice","volume":"4","author":"Lloyd","year":"2002","journal-title":"Neurogenetics"},{"key":"R25","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1073\/pnas.83.8.2310","article-title":"Separation and properties of cellular and scrapie prion proteins","volume":"83","author":"Meyer","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R26","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/ng0298-118","article-title":"Mice with gene targetted prion protein alterations show that Prnp , Sinc and Prni are congruent","volume":"18","author":"Moore","year":"1998","journal-title":"Nat Genet"},{"key":"R27","doi-asserted-by":"crossref","first-page":"10962","DOI":"10.1073\/pnas.90.23.10962","article-title":"Conversion of \u03b1 -helices into \u03b2 -sheets features in the formation of the scrapie prion proteins","volume":"90","author":"Pan","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R28","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/S0896-6273(02)00726-2","article-title":"A change in the conformation of prions accompanies the emergence of a new prion strain","volume":"34","author":"Peretz","year":"2002","journal-title":"Neuron"},{"key":"R29","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1126\/science.1675487","article-title":"Molecular biology of prion diseases","volume":"252","author":"Prusiner","year":"1991","journal-title":"Science"},{"key":"R30","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/2654","article-title":"Eight prion strains PrPSc molecules with different conformations","volume":"4","author":"Safar","year":"1998","journal-title":"Nat Med"},{"key":"R31","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1099\/0022-1317-80-7-1865","article-title":"Host and transmissible spongiform encephalopathy agent strain control glycosylation of PrP","volume":"80","author":"Somerville","year":"1999","journal-title":"J Gen Virol"},{"key":"R32","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/386564a0","article-title":"Biochemical typing of scrapie strains","volume":"386","author":"Somerville","year":"1997","journal-title":"Nature"},{"key":"R33","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1126\/science.274.5295.2079","article-title":"Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity","volume":"274","author":"Telling","year":"1996","journal-title":"Science"},{"key":"R34","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/9030","article-title":"Strain-specific prion-protein conformation determined by metal ions","volume":"1","author":"Wadsworth","year":"1999","journal-title":"Nat Cell Biol"},{"key":"R35","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0140-6736(01)05403-4","article-title":"Tissue distribution of protease resistant prion protein in variant CJD using a highly sensitive immuno-blotting assay","volume":"358","author":"Wadsworth","year":"2001","journal-title":"Lancet"},{"key":"R36","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1136\/vr.142.5.103","article-title":"Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update","volume":"142","author":"Wells","year":"1998","journal-title":"Vet Rec"},{"key":"R37","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/0092-8674(87)90134-6","article-title":"Distinct prion proteins in short and long scrapie incubation period mice","volume":"51","author":"Westaway","year":"1987","journal-title":"Cell"}],"container-title":["Journal of General Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.79889-0?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T14:29:48Z","timestamp":1601994588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.79889-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8,1]]},"references-count":37,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2004,8,1]]}},"URL":"https:\/\/doi.org\/10.1099\/vir.0.79889-0","relation":{},"ISSN":["0022-1317","1465-2099"],"issn-type":[{"value":"0022-1317","type":"print"},{"value":"1465-2099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8,1]]}}}