{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:59:25Z","timestamp":1789181965688,"version":"build-2803163510"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,6,8]]},"abstract":"<jats:p>Human Creutzfeldt\u2013Jakob disease (CJD) and similar neurodegenerative diseases such as sheep scrapie are caused by a variety of related infectious agents. They are associated with abnormal host prion protein (PrP), which is assessed by limited proteolysis to yield resistant PrP bands (PrP-res). Although PrP-res has been posited as the infectious agent, purified PrP-res itself is not infectious. To establish the independence of CJD agent characteristics from those of PrP-res, two different mouse-passaged CJD strains were propagated in neuronal cell lines whose PrP-res patterns differ markedly from each other and from those found in infected brain. In mouse brain, the fast CJD strain, FU, elicits many PrP-res deposits, whereas the slow SY strain elicits few. Both strains evoked PrP-res in cultured murine cells, although SY induced PrP-res only transiently. PrP-res patterns in FU- and SY-infected GT1 cells were identical, and were significantly different from those in brain and in N2a cells. Nevertheless, all FU-infected cell lines reproduced their original fast disease in mice, even after extensive subculture, whereas SY-infected cells produced only slow disease. These data indicate PrP-res neither encodes nor alters agent-specific characteristics. PrP-res was also a poor predictor of infectivity because SY cells that had lost PrP-res were \u224810-fold more infectious than PrP-res-positive cultures. Furthermore, FU titers increased 650-fold, whereas PrP-res remained constant. Passaged FU-infected cells had titers comparable to brain, and &gt;30% of cells displayed abundant cytoplasmic PrP-res aggregates that may trap agent. The continuous substantial replication of CJD in monotypic cells will further the discrimination of agent-specific molecules from pathological host responses to infection.<\/jats:p>","DOI":"10.1073\/pnas.0400158101","type":"journal-article","created":{"date-parts":[[2004,5,25]],"date-time":"2004-05-25T20:43:14Z","timestamp":1085517794000},"page":"8768-8773","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["Two Creutzfeldt\u2013Jakob disease agents reproduce prion protein-independent identities in cell cultures"],"prefix":"10.1073","volume":"101","author":[{"given":"Alvaro","family":"Arjona","sequence":"first","affiliation":[{"name":"Yale Medical School, 333 Cedar Street, Farnum Memorial Basement 11, New Haven, CT 06510; and Nagasaki University School of Medicine, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Simarro","sequence":"additional","affiliation":[{"name":"Yale Medical School, 333 Cedar Street, Farnum Memorial Basement 11, New Haven, CT 06510; and Nagasaki University School of Medicine, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Islinger","sequence":"additional","affiliation":[{"name":"Yale Medical School, 333 Cedar Street, Farnum Memorial Basement 11, New Haven, CT 06510; and Nagasaki University School of Medicine, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Nishida","sequence":"additional","affiliation":[{"name":"Yale Medical School, 333 Cedar Street, Farnum Memorial Basement 11, New Haven, CT 06510; and Nagasaki University School of Medicine, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Manuelidis","sequence":"additional","affiliation":[{"name":"Yale Medical School, 333 Cedar Street, Farnum Memorial Basement 11, New Haven, CT 06510; and Nagasaki University School of Medicine, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,5,25]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1089\/088282403322017875"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.3.871"},{"key":"e_1_3_2_3_2","first-page":"181","volume":"172","year":"1991","unstructured":"Race, R. 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