{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:29:43Z","timestamp":1789691383329,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,2,11]],"date-time":"2016-02-11T00:00:00Z","timestamp":1455148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Prusoff Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Unlike Alzheimer's and most other neurodegenerative diseases, Transmissible Spongiform Encephalopathies (TSEs) are all caused by actively replicating infectious particles of viral size and density. Different strain\u2010specific TSE agents cause CJD, kuru, scrapie and BSE, and all behave as latent viruses that evade adaptive immune responses and can persist for years in lymphoreticular tissues. A foreign viral structure with a nucleic acid genome best explains these TSE strains and their endemic and epidemic spread in susceptible species. Nevertheless, it is widely believed that host prion protein (PrP), without any genetic material, encodes all these strains. We developed rapid infectivity assays that allowed us to reproducibly isolate infectious particles where &gt;85% of the starting titer separated from the majority of host components, including PrP. Remarkably, digestion of all forms of PrP did not reduce brain particle titers. To ask if TSE agents, as other viruses, require nucleic acids, we exposed high titer FU\u2010CJD and 22L scrapie particles to potent nucleases. Both agent\u2010strains were propagated in GT1 neuronal cells to avoid interference by complex degenerative brain changes that can impede nuclease digestions. After exposure to nucleases that are active in sarkosyl, infectivity of both agents was reproducibly reduced by \u226599%. No gold\u2010stained host proteins or any form of PrP were visibly altered by these nucleases. In contrast, co\u2010purifying protected mitochondrial DNA and circular SPHINX DNAs were destroyed. These findings demonstrate that TSE agents require protected genetic material to infect their hosts, and should reopen investigation of essential agent nucleic acids. J. Cell. Biochem. 117: 1947\u20131958, 2016. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.25495","type":"journal-article","created":{"date-parts":[[2016,1,16]],"date-time":"2016-01-16T18:16:16Z","timestamp":1452968176000},"page":"1947-1958","source":"Crossref","is-referenced-by-count":23,"title":["CJD and Scrapie Require Agent\u2010Associated Nucleic Acids for Infection"],"prefix":"10.1002","volume":"117","author":[{"given":"Sotirios","family":"Botsios","sequence":"first","affiliation":[{"name":"Department of Surgery Section of Neuropathology Yale Medical School New Haven 06510 Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Manuelidis","sequence":"additional","affiliation":[{"name":"Department of Surgery Section of Neuropathology Yale Medical School New Haven 06510 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