{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:28:57Z","timestamp":1760956137554,"version":"build-2065373602"},"reference-count":202,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of neurodegenerative protein misfolding diseases that invariably cause death. TSEs occur when the endogenous cellular prion protein (PrPC) misfolds to form the pathological prion protein (PrPSc), which templates further conversion of PrPC to PrPSc, accumulates, and initiates a cascade of pathologic processes in cells and tissues. Different strains of prion disease within a species are thought to arise from the differential misfolding of the prion protein and have different clinical phenotypes. Different strains of prion disease may also result in differential accumulation of PrPSc in brain regions and tissues of natural hosts. Here, we review differential accumulation that occurs in the retinal ganglion cells, cerebellar cortex and white matter, and plexuses of the enteric nervous system in cattle with bovine spongiform encephalopathy, sheep and goats with scrapie, cervids with chronic wasting disease, and humans with prion diseases. By characterizing TSEs in their natural host, we can better understand the pathogenesis of different prion strains. This information is valuable in the pursuit of evaluating and discovering potential biomarkers and therapeutics for prion diseases.<\/jats:p>","DOI":"10.3390\/v13122453","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T20:23:21Z","timestamp":1638908601000},"page":"2453","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Differential Accumulation of Misfolded Prion Strains in Natural Hosts of Prion Diseases"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9828-8097","authenticated-orcid":false,"given":"Zoe J.","family":"Lambert","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, 1800 Christensen, Ames, IA 50011, USA"},{"name":"Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, 1920 Dayton Ave., Ames, IA 50010, USA"},{"name":"Oak Ridge Institute for Science and Education, 1299 Bethel Valley Rd., Oak Ridge, TN 37830, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin J.","family":"Greenlee","sequence":"additional","affiliation":[{"name":"Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, 1920 Dayton Ave., Ames, IA 50010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7130-2650","authenticated-orcid":false,"given":"Eric D.","family":"Cassmann","sequence":"additional","affiliation":[{"name":"Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, 1920 Dayton Ave., Ames, IA 50010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6622-0044","authenticated-orcid":false,"given":"M. Heather","family":"West Greenlee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, 1800 Christensen, Ames, IA 50011, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1126\/science.1675487","article-title":"Molecular biology of prion diseases","volume":"252","author":"Prusiner","year":"1991","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/ana.410200507","article-title":"Creutzfeldt-Jakob disease: Clinical analysis of a consecutive series of 230 neuropathologically verified cases","volume":"20","author":"Brown","year":"1986","journal-title":"Ann. 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