{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T23:25:52Z","timestamp":1774049152603,"version":"3.50.1"},"reference-count":76,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000276","name":"Department of Health and Social Care","doi-asserted-by":"publisher","award":["PR-R17-0916-23006"],"award-info":[{"award-number":["PR-R17-0916-23006"]}],"id":[{"id":"10.13039\/501100000276","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Efforts to prevent human-to-human transmission of variant Creutzfeldt-Jakob disease (vCJD) by contaminated blood would be aided by the development of a sensitive diagnostic test that could be routinely used to screen blood donations. As blood samples from vCJD patients are extremely rare, here we describe the optimisation of real-time quaking-induced conversion (RT-QuIC) for detection of PrP<jats:sup>Sc<\/jats:sup> (misfolded prion protein, a marker of prion infection) in blood samples from an established large animal model of vCJD, sheep experimentally infected with bovine spongiform encephalopathy (BSE). Comparative endpoint titration experiments with RT-QuIC, miniaturized bead protein misfolding cyclic amplification (mb-PMCA) and intracerebral inoculation of a transgenic mouse line expressing sheep PrP (tgOvARQ), demonstrated highly sensitive detection of PrP<jats:sup>Sc<\/jats:sup> by RT-QuIC in a reference sheep brain homogenate. Upon addition of a capture step with iron oxide beads, the RT-QuIC assay was able to detect PrP<jats:sup>Sc<\/jats:sup> in whole blood samples from BSE-infected sheep up to two years before disease onset. Both RT-QuIC and mb-PMCA also demonstrated sensitive detection of PrP<jats:sup>Sc<\/jats:sup> in a reference vCJD-infected human brain homogenate, suggesting that either assay may be suitable for application to human blood samples. Our results support the further development and evaluation of RT-QuIC as a diagnostic or screening test for vCJD.<\/jats:p>","DOI":"10.1371\/journal.pone.0293845","type":"journal-article","created":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T17:55:53Z","timestamp":1698947753000},"page":"e0293845","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Development of a sensitive real-time quaking-induced conversion (RT-QuIC) assay for application in prion-infected blood"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6293-6013","authenticated-orcid":true,"given":"Charlotte M.","family":"Thomas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3319-4035","authenticated-orcid":true,"given":"M. Khalid F.","family":"Salamat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"de Wolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"McCutcheon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Richard Alejo","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean C.","family":"Manson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. Fiona","family":"Houston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"key":"pone.0293845.ref001","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1073\/pnas.95.23.13363","article-title":"Prions","volume":"95","author":"SB Prusiner","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0293845.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. 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