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Prions replicate without a genetic blueprint, but rather contact PrP<jats:sup>C<\/jats:sup>and coerce it to misfold into more prions, which cause neurodegeneration akin to other protein-misfolding diseases like Alzheimer\u2019s disease. A single gene produces two alternatively spliced mRNA transcripts that encode mouse complement receptors CD21\/35, which promote efficient prion replication in the lymphoid system and eventual movement to the brain. Here we show that CD21\/35 are high-affinity prion receptors, but mice expressing only CD21 die from prion disease sooner than CD35-expressing mice, which contain less prions early after infection and exhibit delayed terminal disease, likely due to their less organized splenic follicles. Thus, CD21 appears to be more important for defining splenic architecture that influences prion pathogenesis.<\/jats:p>","DOI":"10.1128\/mspheredirect.00493-17","type":"journal-article","created":{"date-parts":[[2017,11,23]],"date-time":"2017-11-23T01:25:49Z","timestamp":1511400349000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Relative Impact of Complement Receptors CD21\/35 (Cr2\/1) on Scrapie Pathogenesis in Mice"],"prefix":"10.1128","volume":"2","author":[{"given":"Sarah J.","family":"Kane","sequence":"first","affiliation":[{"name":"Prion Research Center, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Swanson","sequence":"additional","affiliation":[{"name":"Prion Research Center, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth O.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Prion Research Center, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah","family":"Rocha","sequence":"additional","affiliation":[{"name":"Prion Research Center, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather R.","family":"Bender","sequence":"additional","affiliation":[{"name":"Prion Research Center, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke R.","family":"Donius","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Medical Oncology, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Aguzzi","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University of Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Hannan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Zabel","sequence":"additional","affiliation":[{"name":"Prion Research Center, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/154.3.518"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/86562"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.9.6144"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/86567"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201579"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxt034"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.4049\/jimmunol.145.9.2974","article-title":"A molecular and immunochemical characterization of mouse CR2. 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