{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:32:56Z","timestamp":1781245976883,"version":"3.54.1"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["PR-R17-0916-23002"],"award-info":[{"award-number":["PR-R17-0916-23002"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00024\/5"],"award-info":[{"award-number":["MC_UU_00024\/5"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00037\/6"],"award-info":[{"award-number":["MC_UU_00037\/6"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The epizootic prion disease of cattle, bovine spongiform encephalopathy (BSE), caused variant Creutzfeldt-Jakob disease (vCJD) in humans following dietary exposure. Codon 129 polymorphism of the human prion protein gene (<jats:italic>PRNP<\/jats:italic>), encoding either methionine (M) or valine (V), dictates the propagation of distinct human prion strains and up to now all but one neuropathologically confirmed vCJD patients have had a 129MM genotype. Concordant with this genetic association, transgenic modelling has established that human PrP 129V is incompatible with the vCJD prion strain and that depending on codon 129 genotype, primary human infection with BSE prions may, in addition to vCJD, result in sporadic CJD-like or novel phenotypes. In 2016 we saw the first neuropathologically confirmed case of vCJD in a patient with a codon 129MV genotype. This patient\u2019s neuropathology and molecular strain type were pathognomonic of vCJD but their clinical presentation and neuroradiological features were more typical of sporadic CJD, suggestive of possible co-propagation of another prion strain. Here we report the transmission properties of prions from the brain and lymphoreticular tissues of the 129MV vCJD patient. Primary transmissions into transgenic mice expressing human PrP with different codon 129 genotypes mainly produced neuropathological and molecular phenotypes congruent to those observed in the same lines of mice challenged with prions from 129MM vCJD patient brain, indicative that the vCJD prion strain was the dominant propagating prion strain in the patient\u2019s brain. Remarkably however, some transgenic mice challenged with 129MV vCJD patient brain propagated a novel prion strain type which at secondary passage was uniformly lethal in mice of all three <jats:italic>PRNP<\/jats:italic> codon 129 genotypes after similar short mean incubation periods. These findings establish that cattle BSE prions can trigger the co-propagation of distinct prion strains in humans.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012904","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T18:32:41Z","timestamp":1740076361000},"page":"e1012904","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Isolation of a novel human prion strain from a PRNP codon 129 heterozygous vCJD patient"],"prefix":"10.1371","volume":"21","author":[{"given":"Fuquan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Joiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline M.","family":"Linehan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florin","family":"Pintilii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamsin","family":"Nazari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Argentina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor","family":"Preston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maged","family":"Taema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Cunningham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel A.","family":"Asante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzehow","family":"Mok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Mead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Brandner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4797-2259","authenticated-orcid":true,"given":"Jonathan D.F.","family":"Wadsworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"issue":"9175","key":"ppat.1012904.ref001","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0140-6736(99)05128-4","article-title":"Variant Creutzfeldt-Jakob disease","volume":"354","author":"J Collinge","year":"1999","journal-title":"Lancet"},{"key":"ppat.1012904.ref002","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.neuro.24.1.519","article-title":"Prion diseases of humans and animals: their causes and molecular basis","volume":"24","author":"J Collinge","year":"2001","journal-title":"Annu Rev Neurosci"},{"issue":"6","key":"ppat.1012904.ref003","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41582-021-00488-7","article-title":"The importance of ongoing international surveillance for Creutzfeldt-Jakob disease","volume":"17","author":"N Watson","year":"2021","journal-title":"Nat Rev Neurol"},{"issue":"9528","key":"ppat.1012904.ref004","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1016\/S0140-6736(06)68930-7","article-title":"Kuru in the 21st century--an acquired human prion disease with very long incubation periods","volume":"367","author":"J Collinge","year":"2006","journal-title":"Lancet"},{"key":"ppat.1012904.ref005","doi-asserted-by":"crossref","first-page":"3386","DOI":"10.1093\/brain\/awv235","article-title":"Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years","volume":"138","author":"P Rudge","year":"2015","journal-title":"Brain"},{"key":"ppat.1012904.ref006","doi-asserted-by":"crossref","unstructured":"Hill AF, Desbruslais M, Joiner S, Sidle KCL, Gowland I, Collinge J, et al. The same prion strain causes vCJD and BSE. 1997;389:448\u201350.","DOI":"10.1038\/38925"},{"key":"ppat.1012904.ref007","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":"EA Asante","year":"2002","journal-title":"EMBO J"},{"key":"ppat.1012904.ref008","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":"JD Wadsworth","year":"2004","journal-title":"Science"},{"key":"ppat.1012904.ref009","doi-asserted-by":"crossref","first-page":"10759","DOI":"10.1073\/pnas.0604292103","article-title":"Dissociation of pathological and molecular phenotype of variant Creutzfeldt-Jakob disease in transgenic human prion protein 129 heterozygous mice","volume":"103","author":"EA Asante","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"issue":"10","key":"ppat.1012904.ref010","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1073\/pnas.0800190105","article-title":"Kuru prions and sporadic Creutzfeldt-Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice","volume":"105","author":"JD Wadsworth","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1510","key":"ppat.1012904.ref011","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1098\/rstb.2008.0069","article-title":"Review. The origin of the prion agent of kuru: molecular and biological strain typing","volume":"363","author":"JD Wadsworth","year":"2008","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"7","key":"ppat.1012904.ref012","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1111\/j.1365-2990.2010.01129.x","article-title":"Contribution of transgenic models to understanding human prion disease","volume":"36","author":"JD Wadsworth","year":"2010","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"1","key":"ppat.1012904.ref013","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s00401-010-0735-5","article-title":"Molecular pathology of human prion disease","volume":"121","author":"JD Wadsworth","year":"2011","journal-title":"Acta Neuropathol"},{"issue":"6067","key":"ppat.1012904.ref014","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1126\/science.1218167","article-title":"Cell biology. 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Joiner","year":"2005","journal-title":"Gut"},{"issue":"3","key":"ppat.1012904.ref039","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1001\/jamaneurol.2013.5378","article-title":"Variant Creutzfeldt-Jakob disease with extremely low lymphoreticular deposition of prion protein","volume":"71","author":"S Mead","year":"2014","journal-title":"JAMA Neurol"},{"issue":"6","key":"ppat.1012904.ref040","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.3201\/eid2606.191116","article-title":"No adaptation of the prion strain in a heterozygous case of variant Creutzfeldt-Jakob disease","volume":"26","author":"A Boyle","year":"2020","journal-title":"Emerg Infect Dis"},{"issue":"9148","key":"ppat.1012904.ref041","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0140-6736(98)12075-5","article-title":"Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples","volume":"353","author":"AF 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