{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:34:37Z","timestamp":1791117277291,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2014,10,2]],"date-time":"2014-10-02T00:00:00Z","timestamp":1412208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Using different prion strains, such as the variant Creutzfeldt-Jakob disease  agent and the atypical bovine spongiform encephalopathy agents, and using transgenic mice expressing human or bovine prion protein, we assessed the reliability of protein misfolding cyclic amplification (PMCA) to model interspecies and genetic barriers to prion  transmission. We compared our PMCA results with in vivo transmission data characterized by attack rates, i.e., the percentage of inoculated mice that developed the disease. Using 19 seed\/substrate combinations, we observed that a significant PMCA amplification was  only obtained when the mouse line used as substrate is susceptible to the corresponding strain. Our results suggest that PMCA provides a useful tool to study genetic barriers to transmission and to study the zoonotic potential of emerging prion strains.<\/jats:p>","DOI":"10.3390\/v6103766","type":"journal-article","created":{"date-parts":[[2014,10,2]],"date-time":"2014-10-02T10:31:31Z","timestamp":1412245891000},"page":"3766-3777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Molecular Modeling of Prion Transmission to Humans"],"prefix":"10.3390","volume":"6","author":[{"given":"Etienne","family":"Levavasseur","sequence":"first","affiliation":[{"name":"Inserm U 1127, CNRS UMR 7225, Sorbonne Universit\u00e9s, UPMC Univ. Paris 06 UMR S 1127,  Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, ICM, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Privat","sequence":"additional","affiliation":[{"name":"Inserm U 1127, CNRS UMR 7225, Sorbonne Universit\u00e9s, UPMC Univ. Paris 06 UMR S 1127,  Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, ICM, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan-Carlos","family":"Martin","sequence":"additional","affiliation":[{"name":"Centro de Investigacion en Sanidad Animal, Carretera de Algete a El Casar, 28130 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Simoneau","sequence":"additional","affiliation":[{"name":"LFB Biom\u00e9dicaments, 91958 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Baron","sequence":"additional","affiliation":[{"name":"Agence nationale de s\u00e9curit\u00e9 sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unit\u00e9 Maladies neurod\u00e9g\u00e9n\u00e9ratives, 69394 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Flan","sequence":"additional","affiliation":[{"name":"LFB Biom\u00e9dicaments, 91958 Les Ulis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan-Maria","family":"Torres","sequence":"additional","affiliation":[{"name":"Centro de Investigacion en Sanidad Animal, Carretera de Algete a El Casar, 28130 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Ha\u00efk","sequence":"additional","affiliation":[{"name":"Inserm U 1127, CNRS UMR 7225, Sorbonne Universit\u00e9s, UPMC Univ. Paris 06 UMR S 1127,  Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, ICM, 75013 Paris, France"},{"name":"AP-HP, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, Cellule nationale de r\u00e9f\u00e9rence des MCJ,  F-75013 Paris, France"},{"name":"AP-HP, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, Neuropathologie, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1073\/pnas.95.23.13363","article-title":"Prions","volume":"95","author":"Prusiner","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/ana.20708","article-title":"Risk factors for variant creutzfeldt-jakob disease: A case-control study","volume":"59","author":"Ward","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/ana.21583","article-title":"Variant creutzfeldt-jakob disease in france and the united kingdom: Evidence for the same agent strain","volume":"65","author":"Brandel","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0140-6736(10)60378-9","article-title":"Variant or sporadic creutzfeldt-jakob disease?","volume":"375","author":"Brandel","year":"2010","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1016\/S0140-6736(09)61568-3","article-title":"Variant cjd in an individual heterozygous for prnp codon 129","volume":"374","author":"Kaski","year":"2009","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/path.2204","article-title":"In vitro amplification and detection of variant creutzfeldt-jakob disease prpsc","volume":"213","author":"Jones","year":"2007","journal-title":"J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.3201\/eid1512.090194","article-title":"Molecular model of prion transmission to humans","volume":"15","author":"Jones","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.cell.2008.07.030","article-title":"Crossing the species barrier by prp(sc) replication in vitro generates unique infectious prions","volume":"134","author":"Castilla","year":"2008","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cell.2005.02.011","article-title":"In vitro generation of infectious scrapie prions","volume":"121","author":"Castilla","year":"2005","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1038\/emboj.2008.181","article-title":"Cell-free propagation of prion strains","volume":"27","author":"Castilla","year":"2008","journal-title":"EMBO J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1000139","DOI":"10.1371\/journal.ppat.1000139","article-title":"Accelerated high fidelity prion amplification within and across prion species barriers","volume":"4","author":"Green","year":"2008","journal-title":"PLoS Pathog."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E1244","DOI":"10.1073\/pnas.1111255108","article-title":"Lower specific infectivity of protease-resistant prion protein generated in cell-free reactions","volume":"108","author":"Klingeborn","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.3201\/eid1412.080941","article-title":"Transmission of atypical bovine prions to mice transgenic for human prion protein","volume":"14","author":"Beringue","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1128\/JVI.02561-07","article-title":"Evaluation of the human transmission risk of an atypical bovine spongiform encephalopathy prion strain","volume":"82","author":"Kong","year":"2008","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e3017","DOI":"10.1371\/journal.pone.0003017","article-title":"Atypical bse (base) transmitted from asymptomatic aging cattle to a primate","volume":"3","author":"Comoy","year":"2008","journal-title":"PLoS One"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3201\/eid1801.111092","article-title":"Oral transmission of l-type bovine spongiform encephalopathy in primate model","volume":"18","author":"Nicot","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_17","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-jakob disease","volume":"101","author":"Casalone","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e1419","DOI":"10.1371\/journal.pone.0001419","article-title":"Prominent and persistent extraneural infection in human prp transgenic mice infected with variant cjd","volume":"3","author":"Beringue","year":"2008","journal-title":"PLoS One"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1001319","DOI":"10.1371\/journal.ppat.1001319","article-title":"Sheep and goat bse propagate more efficiently than cattle bse in human prp transgenic mice","volume":"7","author":"Padilla","year":"2011","journal-title":"PLoS Pathog."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0092-8674(95)90236-8","article-title":"Prion propagation in mice expressing human and chimeric prp transgenes implicates the interaction of cellular prp with another protein","volume":"83","author":"Telling","year":"1995","journal-title":"Cell"},{"key":"ref_21","unstructured":"Torres, J.M. Unpublished."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14279","DOI":"10.1073\/pnas.94.26.14279","article-title":"Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice","volume":"94","author":"Scott","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s00705-002-0958-4","article-title":"Early detection of prpres in bse-infected bovine prp transgenic mice","volume":"148","author":"Castilla","year":"2003","journal-title":"Arch. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1093\/genetics\/165.4.2085","article-title":"Detection of new quantitative trait loci for susceptibility to transmissible spongiform encephalopathies in mice","volume":"165","author":"Moreno","year":"2003","journal-title":"Genetics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8386","DOI":"10.1128\/JVI.00241-11","article-title":"Assessment of the genetic susceptibility of sheep to scrapie by protein misfolding cyclic amplification and comparison with experimental scrapie transmission studies","volume":"85","author":"Bucalossi","year":"2011","journal-title":"J. Virol."},{"key":"ref_26","unstructured":"(Statview, 1998). Statview, version 5 for Windows."},{"key":"ref_27","unstructured":"(2014). XLSSTAT, Addinsoft. version 2014.4.09."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1126\/science.1103932","article-title":"Human prion protein with valine 129 prevents expression of variant cjd phenotype","volume":"306","author":"Wadsworth","year":"2004","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5259","DOI":"10.1128\/JVI.79.9.5259-5271.2005","article-title":"Transmission barriers for bovine, ovine, and human prions in transgenic mice","volume":"79","author":"Scott","year":"2005","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/39057","article-title":"Transmissions to mice indicate that \u201cnew variant\u201d cjd is caused by the bse agent","volume":"389","author":"Bruce","year":"1997","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1371\/journal.ppat.0030031","article-title":"Conversion of the base prion strain into the bse strain: The origin of bse?","volume":"3","author":"Capobianco","year":"2007","journal-title":"PLoS Pathog."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6965","DOI":"10.1523\/JNEUROSCI.0693-07.2007","article-title":"A bovine prion acquires an epidemic bovine spongiform encephalopathy strain-like phenotype on interspecies transmission","volume":"27","author":"Beringue","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4931","DOI":"10.1073\/pnas.94.10.4931","article-title":"Scrapie susceptibility-linked polymorphisms modulate the in vitro conversion of sheep prion protein to protease-resistant forms","volume":"94","author":"Bossers","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1128\/JVI.74.3.1407-1414.2000","article-title":"Susceptibility of sheep for scrapie as assessed by in vitro conversion of nine naturally occurring variants of prp","volume":"74","author":"Bossers","year":"2000","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/40876","article-title":"Molecular assessment of the potential transmissibilities of bse and scrapie to humans","volume":"388","author":"Raymond","year":"1997","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9373","DOI":"10.1074\/jbc.M512239200","article-title":"Conversion efficiency of bank vole prion protein in vitro is determined by residues 155 and 170, but does not correlate with the high susceptibility of bank voles to sheep scrapie in vivo","volume":"281","author":"Piening","year":"2006","journal-title":"J. Biol. Chem."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/6\/10\/3766\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:16:38Z","timestamp":1760217398000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/6\/10\/3766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,2]]},"references-count":36,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,10]]}},"alternative-id":["v6103766"],"URL":"https:\/\/doi.org\/10.3390\/v6103766","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,2]]}}}