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Misfolded host prion protein (PrP\u2010res amyloid) is believed to be the causal infectious agent. However, particles that are stripped of PrP retain both high infectivity and viral proteins not detectable in uninfected mouse controls. We here detail host proteins bound with FU\u2010CJD agent infectious brain particles by proteomic analysis. More than 98 proteins were differentially regulated, and 56 FU\u2010CJD exclusive proteins were revealed after PrP, GFAP, C1q, ApoE, and other late pathologic response proteins were removed. Stripped FU\u2010CJD particles revealed HSC70 (144\u00d7 the uninfected control), cyclophilin B, an FU\u2010CJD exclusive protein required by many viruses, and early endosome\u2010membrane pathways known to facilitate viral processing, replication, and spread. Synaptosomal elements including synapsin\u20102 (at 33\u00d7) and AP180 (a major FU\u2010CJD exclusive protein) paralleled the known ultrastructural location of 25 nm virus\u2010like TSE particles and infectivity in synapses. Proteins without apparent viral or neurodegenerative links (copine\u20103), and others involved in viral\u2010induced protein misfolding and aggregation, were also identified. Human sCJD brain particles contained 146 exclusive proteins, and heat shock, synaptic, and viral pathways were again prominent, in addition to Alzheimer, Parkinson, and Huntington aggregation proteins. Host proteins that bind TSE infectious particles can prevent host immune recognition and contribute to prolonged cross\u2010species transmissions (the species barrier). Our infectious particle strategy, which reduces background sequences by &gt;99%, emphasizes host targets for new therapeutic initiatives. Such therapies can simultaneously subvert common pathways of neurodegeneration.<\/jats:p>","DOI":"10.1002\/pmic.201500059","type":"journal-article","created":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T05:51:04Z","timestamp":1430459464000},"page":"2983-2998","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Proteomic analysis of host brain components that bind to infectious particles in Creutzfeldt\u2010Jakob disease"],"prefix":"10.1002","volume":"15","author":[{"given":"Terry","family":"Kipkorir","sequence":"first","affiliation":[{"name":"Yale University Medical School  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Colangelo","sequence":"additional","affiliation":[{"name":"Yale University Medical School  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Manuelidis","sequence":"additional","affiliation":[{"name":"Yale University Medical School  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905825106"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400158101"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21988"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21090"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.171.3969.389"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-127-32680"},{"key":"e_1_2_8_8_1","first-page":"96","article-title":"Tubulovesicular structures\u2014the ultrastructural hallmark for transmissible spongiform encephalopathies (prion diseases)","volume":"42","author":"Liberski P.","year":"2004","journal-title":"Folia Neuropathol."},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610999104"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1962"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1863-2378.2007.01040.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.23286"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.349691"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-010-0007-0"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24873"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.94"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.09.016"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201400353"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr070325f"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2014.11.002"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac025747h"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1584"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu305"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1118155"},{"key":"e_1_2_8_27_1","first-page":"1","volume-title":"Progress In Neuropathology","author":"Manuelidis E.","year":"1979"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.0033"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/S12035-014-8915-2"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20220"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1356.005"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-014-8544-x"},{"key":"e_1_2_8_33_1","first-page":"367","article-title":"Hsp70 induced by hantavirus infection interacts with viral nucleocapsid protein and its overexpression suppresses virus infection in Vero E6 Cells","volume":"1","author":"Yu L.","year":"2009","journal-title":"Am. 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