{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:57:52Z","timestamp":1773392272092,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"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 transmission into rodents is essential for understanding prion strains. However, it is often limited by a \u201cspecies barrier\u201d that makes transmission challenging and complicates the study of animal and human prion diseases. Here, we report that North American deer mice (Peromyscus maniculatus) are susceptible to infection with both human sporadic Creutzfeldt\u2013Jakob disease (sCJD) and chronic wasting disease (CWD). Experimental transmission of both sCJD and CWD in deer mice resulted in 100% attack rates, albeit with differing incubation times, with CWD-inoculated mice taking nearly three times longer than sCJD-inoculated mice to succumb. We observed distinct patterns of spongiform vacuolation and prion-protein deposition in the brain, as well as distinct protein-glycosylation profiles and seeding kinetics in RT-QuIC for each strain. Adaptation on the second passage led to reduced incubation periods and marked strain-specific pathology, as seen predominantly in the cortex in sCJD and the thalamus in CWD. Notably, primary transmission of CWD resulted in infrequent vacuoles and widespread punctate deposits of prion protein in the brain, while diffuse staining and remarkable vacuolation of the thalamus were seen on passage. Prion seeding kinetics for sCJD and CWD were indistinguishable in the second passage; however, the distinct glycosylation patterns seen on immunoblot of the prion protein were maintained. Adaptation also resulted in extraneural dissemination of prion seeding activity distinct to CWD infection. Overall, the ability to transmit both CWD and sCJD to this model, resulting in clear differences in incubation period, biochemical properties, clinical signs, pathology and seeding kinetics, indicates that the model has the potential for use as a tool to investigate atypical cases of sCJD that may indicate CWD spillover to humans.<\/jats:p>","DOI":"10.3390\/v17040576","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:48:46Z","timestamp":1744850926000},"page":"576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transmission and Characterization of Creutzfeldt\u2013Jakob Disease and Chronic Wasting Disease in the North American Deer Mouse"],"prefix":"10.3390","volume":"17","author":[{"given":"Jennifer","family":"Myskiw","sequence":"first","affiliation":[{"name":"Mycobacteriology, Vector-Borne and Prion Diseases Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lise","family":"Lamoureux","sequence":"additional","affiliation":[{"name":"Mycobacteriology, Vector-Borne and Prion Diseases Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathy","family":"Frost","sequence":"additional","affiliation":[{"name":"Mycobacteriology, Vector-Borne and Prion Diseases Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Fox","sequence":"additional","affiliation":[{"name":"Mycobacteriology, Vector-Borne and Prion Diseases Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9025-8368","authenticated-orcid":false,"given":"Jessy A.","family":"Slota","sequence":"additional","affiliation":[{"name":"Mycobacteriology, Vector-Borne and Prion Diseases Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon","family":"Mitchell","sequence":"additional","affiliation":[{"name":"National and WOAH Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, ON K2H 8P9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben A.","family":"Bailey-Elkin","sequence":"additional","affiliation":[{"name":"Mycobacteriology, Vector-Borne and Prion Diseases Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8108-5955","authenticated-orcid":false,"given":"Stephanie A.","family":"Booth","sequence":"additional","affiliation":[{"name":"Mycobacteriology, Vector-Borne and Prion Diseases Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada"},{"name":"Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.conb.2020.01.009","article-title":"Preclinical biomarkers of prion infection and neurodegeneration","volume":"61","author":"Mok","year":"2020","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rossi, M., Baiardi, S., and Parchi, P. (2019). Understanding Prion Strains: Evidence from Studies of the Disease Forms Affecting Humans. Viruses, 11.","DOI":"10.3390\/v11040309"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"169","DOI":"10.4161\/pri.27836","article-title":"The many shades of prion strain adaptation","volume":"8","author":"Baskakov","year":"2014","journal-title":"Prion"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1128\/JVI.00560-09","article-title":"Chronic Wasting Disease (CWD) Susceptibility of Several North American Rodents That Are Sympatric with Cervid CWD Epidemics","volume":"84","author":"Heisey","year":"2010","journal-title":"J. Virol."},{"key":"ref_5","unstructured":"Hall, E.R. (1981). The Mammals of North America, Wiley. Available online: http:\/\/archive.org\/details\/mammalsofnortham0000hall."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Burke, C.M., Mark, K.M.K., Walsh, D.J., Noble, G.P., Steele, A.D., Diack, A.B., Manson, J.C., Watts, J.C., and Supattapone, S. (2020). Identification of a homology-independent linchpin domain controlling mouse and bank vole prion protein conversion. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008875"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Arshad, H., Patel, Z., Al-Azzawi, Z.A.M., Amano, G., Li, L., Mehra, S., Eid, S., Schmitt-Ulms, G., and Watts, J.C. (2024). The molecular determinants of a universal prion acceptor. PLoS Pathog., 20.","DOI":"10.1101\/2024.03.01.582976"},{"key":"ref_8","first-page":"123","article-title":"Chronic Wasting Disease In Cervids: Prevalence, Impact And Management Strategies","volume":"10","author":"Rivera","year":"2019","journal-title":"Vet. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13794","DOI":"10.1128\/JVI.79.21.13794-13796.2005","article-title":"Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus)","volume":"79","author":"Marsh","year":"2005","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00550-18","DOI":"10.1128\/JVI.00550-18","article-title":"Lack of Transmission of Chronic Wasting Disease to Cynomolgus Macaques","volume":"92","author":"Race","year":"2018","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"19841","DOI":"10.1074\/jbc.R114.550707","article-title":"Mouse Models for Studying the Formation and Propagation of Prions","volume":"289","author":"Watts","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1093\/infdis\/jiab033","article-title":"Humanized Transgenic Mice Are Resistant to Chronic Wasting Disease Prions From Norwegian Reindeer and Moose","volume":"226","author":"Wadsworth","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1017\/cjn.2020.139","article-title":"Prospective Study Demonstrates Utility of EP-QuIC in Creutzfeldt\u2013Jakob Disease Diagnoses","volume":"48","author":"Simon","year":"2021","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1128\/JCM.00542-16","article-title":"Endpoint Quaking-Induced Conversion: A Sensitive, Specific, and High-Throughput Method for Antemortem Diagnosis of Creutzfeldt-Jacob Disease","volume":"54","author":"Cheng","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","first-page":"1241","article-title":"Epidemiology of an outbreak of chronic wasting disease on elk farms in Saskatchewan","volume":"48","author":"Argue","year":"2007","journal-title":"Can. Vet. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1136\/vr.155.10.295","article-title":"Variable patterns of distribution of PrPCWD in the obex and cranial lymphoid tissues of Rocky Mountain elk (Cervus elaphus nelsoni) with subclinical chronic wasting disease","volume":"155","author":"Spraker","year":"2004","journal-title":"Vet. Rec."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0021-9975(68)90006-6","article-title":"The sequential development of the brain lesions of scrapie in three strains of mice","volume":"78","author":"Fraser","year":"1968","journal-title":"J. Comp. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1021\/cb5006239","article-title":"Mechanism of Scrapie Prion Precipitation with Phosphotungstate Anions","volume":"10","author":"Levine","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E4949","DOI":"10.1073\/pnas.1513426112","article-title":"Propagation of prions causing synucleinopathies in cultured cells","volume":"112","author":"Woerman","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100029","DOI":"10.1016\/j.labinv.2022.100029","article-title":"Development of an Automated Capillary Immunoassay to Detect Prion Glycotypes in Creutzfeldt-Jakob Disease","volume":"103","author":"Myskiw","year":"2023","journal-title":"Lab. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/978-1-4939-7244-9_14","article-title":"RT-QuIC Assays for Prion Disease Detection and Diagnostics","volume":"1658","author":"Groveman","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W","article-title":"Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects","volume":"46","author":"Parchi","year":"1999","journal-title":"Ann. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"31417","DOI":"10.1073\/pnas.2013237117","article-title":"Studies in bank voles reveal strain differences between chronic wasting disease prions from Norway and North America","volume":"117","author":"Nonno","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1329010","DOI":"10.3389\/fnins.2024.1329010","article-title":"Multiple steps of prion strain adaptation to a new host","volume":"18","author":"Bocharova","year":"2024","journal-title":"Front. Neurosci"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Watts, J.C., Giles, K., Patel, S., Oehler, A., De Armond, S.J., and Prusiner, S.B. (2014). Evidence that bank vole PrP is a universal acceptor for prions. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1003990"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1099\/vir.0.2008\/005520-0","article-title":"The bank vole (Myodes glareolus) as a sensitive bioassay for sheep scrapie","volume":"89","author":"Chianini","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Agrimi, U., Nonno, R., Dell\u2019Omo, G., Di Bari, M.A., Conte, M., Chiappini, B., Esposito, E., Di Guardo, G., Windl, O., and Vaccari, G. (2008). Prion protein amino acid determinants of differential susceptibility and molecular feature of prion strains in mice and voles. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000113"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Di Bari, M.A., Nonno, R., Castilla, J., D\u2019Agostino, C., Pirisinu, L., Riccardi, G., Conte, M., Richt, J., Kunkle, R., and Langeveld, J. (2013). Chronic wasting disease in bank voles: Characterisation of the shortest incubation time model for prion diseases. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003219"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1004983","DOI":"10.1371\/journal.ppat.1004983","article-title":"Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains","volume":"11","author":"Groveman","year":"2015","journal-title":"PLoS Pathog."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1126\/science.1187107","article-title":"Prion Strain Mutation Determined by Prion Protein Conformational Compatibility and Primary Structure","volume":"328","author":"Angers","year":"2010","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nonno, R., Bari, M.A.D., Cardone, F., Vaccari, G., Fazzi, P., Dell\u2019Omo, G., Cartoni, C., Ingrosso, L., Boyle, A., and Galeno, R. (2006). Efficient Transmission and Characterization of Creutzfeldt\u2013Jakob Disease Strains in Bank Voles. PLOS Pathog., 2.","DOI":"10.1371\/journal.ppat.0020012"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1093\/brain\/awq234","article-title":"Agent strain variation in human prion disease: Insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease","volume":"133","author":"Parchi","year":"2010","journal-title":"Brain"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4784","DOI":"10.1073\/pnas.2627989100","article-title":"Abbreviated incubation times for human prions in mice expressing a chimeric mouse-human prion protein transgene","volume":"100","author":"Korth","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12005","DOI":"10.1073\/pnas.1004688107","article-title":"Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties","volume":"107","author":"Bishop","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"19076","DOI":"10.1074\/jbc.M117.794107","article-title":"Asparagine and glutamine ladders promote cross-species prion conversion","volume":"292","author":"Kurt","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/bpa.12638","article-title":"A domain responsible for spontaneous conversion of bank vole prion protein","volume":"29","author":"Kobayashi","year":"2018","journal-title":"Brain Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Arshad, H., Eid, S., Mehra, S., Williams, D., Kaczmarczyk, L., Stuart, E., Jackson, W.S., Schmitt-Ulms, G., and Watts, J.C. (2024). The Brain Interactome of a Permissive Prion Replication Substrate. bioRxiv, bioRxiv:2024.08.19.608704.","DOI":"10.1101\/2024.08.19.608704"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/4\/576\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:16:00Z","timestamp":1760030160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/4\/576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,16]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["v17040576"],"URL":"https:\/\/doi.org\/10.3390\/v17040576","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,16]]}}}