{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:33:27Z","timestamp":1789875207957,"version":"4.0.1"},"reference-count":72,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T00:00:00Z","timestamp":1530748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS069566"],"award-info":[{"award-number":["NS069566"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS076896"],"award-info":[{"award-number":["NS076896"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008054","name":"Ram\u00f3n Areces Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2015-04521"],"award-info":[{"award-number":["2015-04521"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2015-05868"],"award-info":[{"award-number":["2015-05868"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The G\u00f6ran Gustafsson Foundation"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Prions typically spread into the central nervous system (CNS), likely via peripheral nerves. Yet prion conformers differ in their capacity to penetrate the CNS; certain fibrillar prions replicate persistently in lymphoid tissues with no CNS entry, leading to chronic silent carriers. Subclinical carriers of variant Creutzfeldt\u2013Jakob (vCJD) prions in the United Kingdom have been estimated at 1:2000, and vCJD prions have been transmitted through blood transfusion, however, the circulating prion conformers that neuroinvade remain unclear. Here we investigate how prion conformation impacts brain entry of transfused prions by challenging mice intravenously to subfibrillar and fibrillar strains. We show that most strains infiltrated the brain and caused terminal disease, however, the fibrillar prions showed reduced CNS entry in a strain\u2010dependent manner. Strikingly, the highly fibrillar mCWD prion strain replicated in the spleen and emerged in the brain as a novel strain, indicating that a new neuroinvasive prion had been generated from a previously non\u2010neuroinvasive strain. The new strain showed altered plaque morphology, brain regions targeted and biochemical properties and these properties were maintained upon intracerebral passage. Intracerebral passage of prion\u2010infected spleen re\u2010created the new strain. Splenic prions resembled the new strain biochemically and intracerebral passage of prion\u2010infected spleen re\u2010created the new strain, collectively suggesting splenic prion replication as a potential source. Taken together, these results indicate that intravenous exposure to prion\u2010contaminated blood or blood products may generate novel neuroinvasive prion conformers and disease phenotypes, potentially arising from prion replication in non\u2010neural tissues or from conformer selection.<\/jats:p>","DOI":"10.1111\/bpa.12598","type":"journal-article","created":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T09:42:51Z","timestamp":1520242971000},"page":"999-1011","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Generation of novel neuroinvasive prions following intravenous challenge"],"prefix":"10.1111","volume":"28","author":[{"given":"Patricia","family":"Aguilar\u2010Calvo","sequence":"first","affiliation":[{"name":"Departments of Pathology and Medicine UC San Diego La Jolla CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus","family":"Bett","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine UC San Diego La Jolla CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro M.","family":"Sevillano","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine UC San Diego La Jolla CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Kurt","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine UC San Diego La Jolla CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine UC San Diego La Jolla CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Soldau","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine UC San Diego La Jolla CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Hammarstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Physics, Chemistry, and Biology Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Peter R.","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Physics, Chemistry, and Biology Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-0965","authenticated-orcid":false,"given":"Christina J.","family":"Sigurdson","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine UC San Diego La Jolla CA"},{"name":"Department of Pathology, Microbiology, and Immunology UC Davis Davis 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