{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:54:26Z","timestamp":1760151266032,"version":"build-2065373602"},"reference-count":125,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transmissible spongiform encephalopathies or prion disorders are fatal infectious diseases that cause characteristic spongiform degeneration in the central nervous system. The causative agent, the so-called prion, is an unconventional infectious agent that propagates by converting the host-encoded cellular prion protein PrP into ordered protein aggregates with infectious properties. Prions are devoid of coding nucleic acid and thus rely on the host cell machinery for propagation. While it is now established that, in addition to PrP, other cellular factors or processes determine the susceptibility of cell lines to prion infection, exact factors and cellular processes remain broadly obscure. Still, cellular models have uncovered important aspects of prion propagation and revealed intercellular dissemination strategies shared with other intracellular pathogens. Here, we summarize what we learned about the processes of prion invasion, intracellular replication and subsequent dissemination from ex vivo cell models.<\/jats:p>","DOI":"10.3390\/ijms23062909","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T12:35:37Z","timestamp":1646742937000},"page":"2909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Propagation and Dissemination Strategies of Transmissible Spongiform Encephalopathy Agents in Mammalian Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"Stefanie-Elisabeth","family":"Heum\u00fcller","sequence":"first","affiliation":[{"name":"Laboratory of Prion Cell Biology, German Center for Neurodegenerative Diseases Bonn (DZNE e.V.), Venusberg-Campus 1\/99, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika C.","family":"Hornberger","sequence":"additional","affiliation":[{"name":"Laboratory of Prion Cell Biology, German Center for Neurodegenerative Diseases Bonn (DZNE e.V.), Venusberg-Campus 1\/99, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4147-7919","authenticated-orcid":false,"given":"Alina S.","family":"Hebestreit","sequence":"additional","affiliation":[{"name":"Laboratory of Prion Cell Biology, German Center for Neurodegenerative Diseases Bonn (DZNE e.V.), Venusberg-Campus 1\/99, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Hossinger","sequence":"additional","affiliation":[{"name":"Laboratory of Prion Cell Biology, German Center for Neurodegenerative Diseases Bonn (DZNE e.V.), Venusberg-Campus 1\/99, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0583-4015","authenticated-orcid":false,"given":"Ina M.","family":"Vorberg","sequence":"additional","affiliation":[{"name":"Laboratory of Prion Cell Biology, German Center for Neurodegenerative Diseases Bonn (DZNE e.V.), Venusberg-Campus 1\/99, 53127 Bonn, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Rheinische Friedrich-Wilhelms-Universit\u00e4t Bonn, Siegmund-Freud-Str. 25, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.5455\/OVJ.2021.v11.i4.23","article-title":"Animal prion diseases: A review of intraspecies transmission","volume":"11","author":"Gallardo","year":"2021","journal-title":"Open Vet. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1126\/science.6801762","article-title":"Novel proteinaceous infectious particles cause scrapie","volume":"216","author":"Prusiner","year":"1982","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/0092-8674(85)90333-2","article-title":"A cellular gene encodes scrapie PrP 27-30 protein","volume":"40","author":"Oesch","year":"1985","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/375698a0","article-title":"Non-genetic propagation of strain-specific properties of scrapie prion protein","volume":"375","author":"Bessen","year":"1995","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/bs.pmbts.2020.07.009","article-title":"Cofactor molecules: Essential partners for infectious prions","volume":"175","author":"Supattapone","year":"2020","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Burke, C.M., Walsh, D.J., Mark, K.M.K., Deleault, N.R., Nishina, K.A., Agrimi, U., Di Bari, M.A., and Supattapone, S. (2020). Cofactor and glycosylation preferences for in vitro prion conversion are predominantly determined by strain conformation. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008495"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.vetimm.2008.04.002","article-title":"Enrichment of prion protein in exosomes derived from ovine cerebral spinal fluid","volume":"124","author":"Vella","year":"2008","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1093\/emboj\/cdg344","article-title":"The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein","volume":"22","author":"Sunyach","year":"2003","journal-title":"EMBO J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6923","DOI":"10.1038\/s41598-017-07260-2","article-title":"Prion strains depend on different endocytic routes for productive infection","volume":"7","author":"Fehlinger","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pineau, H., and Sim, V.L. (2021). From Cell Culture to Organoids-Model Systems for Investigating Prion Strain Characteristics. Biomolecules, 11.","DOI":"10.3390\/biom11010106"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"23782","DOI":"10.1074\/jbc.M802433200","article-title":"Prions impair bioaminergic functions through serotonin- or catecholamine-derived neurotoxins in neuronal cells","volume":"283","author":"Nishida","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11572","DOI":"10.1074\/jbc.RA120.012596","article-title":"An astrocyte cell line that differentially propagates murine prions","volume":"295","author":"Tahir","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.15252\/embj.201387150","article-title":"Identification of a gene regulatory network associated with prion replication","volume":"33","author":"Marbiah","year":"2014","journal-title":"EMBO J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vorberg, I.M. (2019). All the Same? The Secret Life of Prion Strains within Their Target Cells. Viruses, 11.","DOI":"10.3390\/v11040334"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Marijanovic, Z., Caputo, A., Campana, V., and Zurzolo, C. (2009). Identification of an intracellular site of prion conversion. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000426"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1083\/jcb.110.3.743","article-title":"Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells","volume":"110","author":"Borchelt","year":"1990","journal-title":"J. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mattei, V., Barenco, M.G., Tasciotti, V., Garofalo, T., Longo, A., Boller, K., Lower, J., Misasi, R., Montrasio, F., and Sorice, M. (2009). Paracrine diffusion of PrP(C) and propagation of prion infectivity by plasma membrane-derived microvesicles. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005057"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1042\/BC20080025","article-title":"Mouse neuroblastoma cells release prion infectivity associated with exosomal vesicles","volume":"100","author":"Alais","year":"2008","journal-title":"Biol. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/bmb\/66.1.1","article-title":"Introduction to the transmissible spongiform encephalopathies or prion diseases","volume":"66","author":"Chesebro","year":"2003","journal-title":"Br. Med. Bull."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10962","DOI":"10.1073\/pnas.90.23.10962","article-title":"Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins","volume":"90","author":"Pan","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41594-021-00565-x","article-title":"Scaling analysis reveals the mechanism and rates of prion replication in vivo","volume":"28","author":"Meisl","year":"2021","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1093\/oxfordjournals.bmb.a072649","article-title":"Scrapie strain variation and mutation","volume":"49","author":"Bruce","year":"1993","journal-title":"Br. Med. Bull."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7859","DOI":"10.1128\/jvi.68.12.7859-7868.1994","article-title":"Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy","volume":"68","author":"Bessen","year":"1994","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/ncb1841","article-title":"Prions hijack tunnelling nanotubes for intercellular spread","volume":"11","author":"Safar","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/2654","article-title":"Eight prion strains have PrP(Sc) molecules with different conformations","volume":"4","author":"Safar","year":"1998","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1007\/s00018-014-1735-8","article-title":"Prion strains are differentially released through the exosomal pathway","volume":"72","author":"Huor","year":"2015","journal-title":"Cell Mol. Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0960-9822(02)00722-4","article-title":"Transfer of scrapie prion infectivity by cell contact in culture","volume":"12","author":"Kanu","year":"2002","journal-title":"Curr. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"374","DOI":"10.3390\/v5010374","article-title":"Cellular aspects of prion replication in vitro","volume":"5","author":"Grassmann","year":"2013","journal-title":"Viruses"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fmolb.2017.00019","article-title":"Physiological Functions of the Cellular Prion Protein","volume":"4","author":"Castle","year":"2017","journal-title":"Front. Mol Biosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"762918","DOI":"10.3389\/fnmol.2021.762918","article-title":"PrP (C) as a Transducer of Physiological and Pathological Signals","volume":"14","author":"Panes","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5611","DOI":"10.21873\/anticanres.14574","article-title":"Role of PrP(C) in Cancer Stem Cell Characteristics and Drug Resistance in Colon Cancer Cells","volume":"40","author":"Go","year":"2020","journal-title":"Anticancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1111\/brv.12731","article-title":"The IDIP framework for assessing protein function and its application to the prion protein","volume":"96","author":"Mehrabian","year":"2021","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/09687860500449994","article-title":"The prion protein and lipid rafts","volume":"23","author":"Taylor","year":"2006","journal-title":"Mol. Membr. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1038\/sj.emboj.7601162","article-title":"Retrovirus infection strongly enhances scrapie infectivity release in cell culture","volume":"25","author":"Leblanc","year":"2006","journal-title":"EMBO J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4338","DOI":"10.1111\/febs.12196","article-title":"Roles of endoproteolytic alpha-cleavage and shedding of the prion protein in neurodegeneration","volume":"280","author":"Altmeppen","year":"2013","journal-title":"FEBS J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14793","DOI":"10.1074\/jbc.270.24.14793","article-title":"The N-terminal domain of a glycolipid-anchored prion protein is essential for its endocytosis via clathrin-coated pits","volume":"270","author":"Shyng","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14945","DOI":"10.1073\/pnas.93.25.14945","article-title":"Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains","volume":"93","author":"Vey","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Uchiyama, K., Tomita, M., Yano, M., Chida, J., Hara, H., Das, N.R., Nykjaer, A., and Sakaguchi, S. (2017). Prions amplify through degradation of the VPS10P sorting receptor sortilin. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006470"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8262","DOI":"10.1073\/pnas.87.21.8262","article-title":"Acquisition of protease resistance by prion proteins in scrapie-infected cells does not require asparagine-linked glycosylation","volume":"87","author":"Taraboulos","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.neuron.2018.08.010","article-title":"Muskelin Coordinates PrP(C) Lysosome versus Exosome Targeting and Impacts Prion Disease Progression","volume":"99","author":"Heisler","year":"2018","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1128\/jvi.63.1.175-181.1989","article-title":"Prion protein biosynthesis in scrapie-infected and uninfected neuroblastoma cells","volume":"63","author":"Caughey","year":"1989","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1128\/JVI.01379-06","article-title":"Microglial cell line established from prion protein-overexpressing mice is susceptible to various murine prion strains","volume":"81","author":"Iwamaru","year":"2007","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"18217","DOI":"10.1016\/S0021-9258(18)55257-1","article-title":"The scrapie-associated form of PrP is made from a cell surface precursor that is both protease- and phospholipase-sensitive","volume":"266","author":"Caughey","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev.biochem.78.082907.145410","article-title":"Getting a grip on prions: Oligomers, amyloids, and pathological membrane interactions","volume":"78","author":"Caughey","year":"2009","journal-title":"Annu. Rev. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"12952","DOI":"10.1038\/s41598-020-69657-w","article-title":"Publisher Correction: Global analysis of protein degradation in prion infected cells","volume":"10","author":"Hutti","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/j.1750-3639.1998.tb00171.x","article-title":"The prion diseases","volume":"8","author":"Prusiner","year":"1998","journal-title":"Brain Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11666","DOI":"10.1073\/pnas.1834432100","article-title":"A quantitative, highly sensitive cell-based infectivity assay for mouse scrapie prions","volume":"100","author":"Klohn","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1128\/JVI.74.1.320-325.2000","article-title":"Successful transmission of three mouse-adapted scrapie strains to murine neuroblastoma cell lines overexpressing wild-type mouse prion protein","volume":"74","author":"Nishida","year":"2000","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sarnataro, D., Caputo, A., Casanova, P., Puri, C., Paladino, S., Tivodar, S.S., Campana, V., Tacchetti, C., and Zurzolo, C. (2009). Lipid rafts and clathrin cooperate in the internalization of PrP in epithelial FRT cells. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005829"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8821","DOI":"10.1128\/jvi.71.11.8821-8831.1997","article-title":"A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis","volume":"71","author":"Schatzl","year":"1997","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9683","DOI":"10.1073\/pnas.0308413101","article-title":"Cells release prions in association with exosomes","volume":"101","author":"Fevrier","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1099\/0022-1317-68-5-1391","article-title":"Characterization of scrapie infection in mouse neuroblastoma cells","volume":"68","author":"Race","year":"1987","journal-title":"J. Gen. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12271","DOI":"10.1073\/pnas.0402725101","article-title":"Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death","volume":"101","author":"Cronier","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1128\/JVI.78.1.482-490.2004","article-title":"Cultured peripheral neuroglial cells are highly permissive to sheep prion infection","volume":"78","author":"Archer","year":"2004","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4055","DOI":"10.1073\/pnas.061337998","article-title":"Ex vivo propagation of infectious sheep scrapie agent in heterologous epithelial cells expressing ovine prion protein","volume":"98","author":"Vilette","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Miyazawa, K., Masujin, K., Okada, H., Ushiki-Kaku, Y., Matsuura, Y., and Yokoyama, T. (2017). Selective propagation of mouse-passaged scrapie prions with long incubation period from a mixed prion population using GT1-7 cells. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179317"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11151","DOI":"10.1038\/s41598-019-47629-z","article-title":"Gene-edited murine cell lines for propagation of chronic wasting disease prions","volume":"9","author":"Walia","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1128\/JVI.80.2.596-604.2006","article-title":"Inhibition of protease-resistant prion protein formation in a transformed deer cell line infected with chronic wasting disease","volume":"80","author":"Raymond","year":"2006","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"8322","DOI":"10.1128\/JVI.00633-10","article-title":"Cell-based quantification of chronic wasting disease prions","volume":"84","author":"Bian","year":"2010","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1093\/infdis\/jit623","article-title":"Cycline efficacy on the propagation of human prions in primary cultured neurons is strain-specific","volume":"209","author":"Hannaoui","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"20908","DOI":"10.1073\/pnas.0710054104","article-title":"Prion strain discrimination in cell culture: The cell panel assay","volume":"104","author":"Mahal","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41556-018-0250-9","article-title":"Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication","volume":"21","author":"Mathieu","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_65","first-page":"1345","article-title":"4-hydroxytamoxifen leads to PrPSc clearance by conveying both PrPC and PrPSc to lysosomes independently of autophagy","volume":"126","author":"Marzo","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4261","DOI":"10.1038\/s41467-020-18081-9","article-title":"ITGB3-mediated uptake of small extracellular vesicles facilitates intercellular communication in breast cancer cells","volume":"11","author":"Fuentes","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"17380","DOI":"10.1073\/pnas.1304266110","article-title":"Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity","volume":"110","author":"Christianson","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1038\/nm1105-1137","article-title":"PrPSc in mammary glands of sheep affected by scrapie and mastitis","volume":"11","author":"Ligios","year":"2005","journal-title":"Nat. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1086\/381166","article-title":"Susceptibility of common fibroblast cell lines to transmissible spongiform encephalopathy agents","volume":"189","author":"Vorberg","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10109","DOI":"10.1038\/s41598-021-89586-6","article-title":"Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells","volume":"11","author":"Hara","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1093\/emboj\/20.13.3351","article-title":"Scrapie strains maintain biological phenotypes on propagation in a cell line in culture","volume":"20","author":"Birkett","year":"2001","journal-title":"EMBO J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/infdis\/167.1.7","article-title":"Brain regional distribution of prion protein PrP27-30 in mice stereotaxically microinjected with different strains of scrapie","volume":"167","author":"Kascsak","year":"1993","journal-title":"J. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.ceb.2008.03.005","article-title":"Intercellular transfer mediated by tunneling nanotubes","volume":"20","author":"Gerdes","year":"2008","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5207","DOI":"10.1523\/JNEUROSCI.0653-05.2005","article-title":"Uptake and neuritic transport of scrapie prion protein coincident with infection of neuronal cells","volume":"25","author":"Magalhaes","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e01686","DOI":"10.1128\/JVI.01686-16","article-title":"PrP Knockout Cells Expressing Transmembrane PrP Resist Prion Infection","volume":"91","author":"Marshall","year":"2017","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"24722","DOI":"10.3402\/jev.v3.24722","article-title":"Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons","volume":"3","author":"Chivet","year":"2014","journal-title":"J. Extracell Vesicles"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Leblanc, P., Hasenkrug, K., Ward, A., Myers, L., Messer, R.J., Alais, S., Timmes, A., and Priola, S.A. (2012). Co-infection with the friend retrovirus and mouse scrapie does not alter prion disease pathogenesis in susceptible mice. PLoS ONE, 7.","DOI":"10.1371\/annotation\/c6b9e78a-451b-4a34-bcd3-24a820bfa32f"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1128\/jvi.62.5.1558-1564.1988","article-title":"Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins","volume":"62","author":"Butler","year":"1988","journal-title":"J. Virol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1099\/0022-1317-65-12-2191","article-title":"In vitro replication of scrapie agent in a neuronal model: Infection of PC12 cells","volume":"65","author":"Rubenstein","year":"1984","journal-title":"J. Gen. Virol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1128\/JVI.03082-12","article-title":"Prion propagation and toxicity occur in vitro with two-phase kinetics specific to strain and neuronal type","volume":"87","author":"Hannaoui","year":"2013","journal-title":"J. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/S0034-5288(18)34291-7","article-title":"Multiplication of scrapie agent in cell culture","volume":"11","author":"Clarke","year":"1970","journal-title":"Res. Vet. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"13147","DOI":"10.1073\/pnas.1000784107","article-title":"Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR","volume":"107","author":"Roffe","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1242\/jcs.058099","article-title":"Neuronal low-density lipoprotein receptor-related protein 1 binds and endocytoses prion fibrils via receptor cluster 4","volume":"123","author":"Jen","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1096\/fj.11-202077","article-title":"Prion-infected cells regulate the release of exosomes with distinct ultrastructural features","volume":"26","author":"Coleman","year":"2012","journal-title":"FASEB J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5739","DOI":"10.1038\/s41467-021-25855-2","article-title":"Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions","volume":"12","author":"Liu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.1074\/jbc.RA118.007135","article-title":"Engineering a murine cell line for the stable propagation of hamster prions","volume":"294","author":"Bourkas","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1099\/vir.0.83344-0","article-title":"A cell line infectible by prion strains from different species","volume":"89","author":"Courageot","year":"2008","journal-title":"J Gen Virol"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1074\/jbc.M115.684258","article-title":"Stimulating the Release of Exosomes Increases the Intercellular Transfer of Prions","volume":"291","author":"Guo","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.virol.2016.05.014","article-title":"Complement factors alter the amount of PrP(Sc) in primary-cultured mouse cortical neurons associated with increased membrane permeability","volume":"496","author":"Hasebe","year":"2016","journal-title":"Virology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1084\/jem.20161547","article-title":"Human stem cell-derived astrocytes replicate human prions in a PRNP genotype-dependent manner","volume":"214","author":"Krejciova","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1128\/jvi.76.5.2434-2439.2002","article-title":"PrP expression and replication by Schwann cells: Implications in prion spreading","volume":"76","author":"Follet","year":"2002","journal-title":"J. Virol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"13794","DOI":"10.1128\/JVI.01502-07","article-title":"Prion strain- and species-dependent effects of antiprion molecules in primary neuronal cultures","volume":"81","author":"Cronier","year":"2007","journal-title":"J. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/path.2145","article-title":"Packaging of prions into exosomes is associated with a novel pathway of PrP processing","volume":"211","author":"Vella","year":"2007","journal-title":"J. Pathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1126\/science.1118155","article-title":"Reciprocal interference between specific CJD and scrapie agents in neural cell cultures","volume":"310","author":"Nishida","year":"2005","journal-title":"Science"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"8768","DOI":"10.1073\/pnas.0400158101","article-title":"Two Creutzfeldt-Jakob disease agents reproduce prion protein-independent identities in cell cultures","volume":"101","author":"Arjona","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.virusres.2017.07.016","article-title":"Correlation of cellular factors and differential scrapie prion permissiveness in ovine microglia","volume":"240","author":"Dinkel","year":"2017","journal-title":"Virus Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5102","DOI":"10.1093\/hmg\/ddu233","article-title":"In vitro screen of prion disease susceptibility genes using the scrapie cell assay","volume":"23","author":"Brown","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4377","DOI":"10.1128\/JVI.74.9.4377-4386.2000","article-title":"Cultured cell sublines highly susceptible to prion infection","volume":"74","author":"Bosque","year":"2000","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Philiastides, A., Ribes, J.M., Yip, D.C., Schmidt, C., Benilova, I., and Klohn, P.C. (2019). A New Cell Model for Investigating Prion Strain Selection and Adaptation. Viruses, 11.","DOI":"10.3390\/v11100888"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1292\/jvms.12-0061","article-title":"Establishment of a cell line persistently infected with chronic wasting disease prions","volume":"74","author":"Kim","year":"2012","journal-title":"J. Vet. Med. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1016\/j.biocel.2008.05.024","article-title":"Mouse-adapted sporadic human Creutzfeldt-Jakob disease prions propagate in cell culture","volume":"40","author":"Lawson","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Tark, D., Kim, H., Neale, M.H., Kim, M., Sohn, H., Lee, Y., Cho, I., Joo, Y., and Windl, O. (2015). Generation of a persistently infected MDBK cell line with natural bovine spongiform encephalopathy (BSE). PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0115939"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1128\/JVI.80.5.2106-2117.2006","article-title":"Mouse-adapted scrapie infection of SN56 cells: Greater efficiency with microsome-associated versus purified PrP-res","volume":"80","author":"Baron","year":"2006","journal-title":"J. Virol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.virol.2008.07.006","article-title":"Acute cellular uptake of abnormal prion protein is cell type and scrapie-strain independent","volume":"379","author":"Greil","year":"2008","journal-title":"Virology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1016\/j.celrep.2020.01.098","article-title":"Entropic Bristles Tune the Seeding Efficiency of Prion-Nucleating Fragments","volume":"30","author":"Michiels","year":"2020","journal-title":"Cell Rep."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Walzlein, J.H., Schwenke, K.A., and Beekes, M. (2021). Propagation of CJD Prions in Primary Murine Glia Cells Expressing Human PrP(c). Pathogens, 10.","DOI":"10.3390\/pathogens10081060"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/19336896.2016.1181250","article-title":"Physical, chemical and kinetic factors affecting prion infectivity","volume":"10","author":"Properzi","year":"2016","journal-title":"Prion"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"17062","DOI":"10.1074\/jbc.M500122200","article-title":"Heparan sulfate is a cellular receptor for purified infectious prions","volume":"280","author":"Horonchik","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"9853","DOI":"10.1128\/JVI.01276-15","article-title":"Modulation of Glycosaminoglycans Affects PrPSc Metabolism but Does Not Block PrPSc Uptake","volume":"89","author":"Wolf","year":"2015","journal-title":"J. Virol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/sj.embor.embor768","article-title":"The 37 kDa\/67 kDa laminin receptor is required for PrP(Sc) propagation in scrapie-infected neuronal cells","volume":"4","author":"Leucht","year":"2003","journal-title":"EMBO Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"20762","DOI":"10.1038\/srep20762","article-title":"Astrocyte-to-neuron intercellular prion transfer is mediated by cell-cell contact","volume":"6","author":"Victoria","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.virol.2013.11.007","article-title":"Characterization of intracellular dynamics of inoculated PrP-res and newly generated PrP(Sc) during early stage prion infection in Neuro2a cells","volume":"450\u2013451","author":"Yamasaki","year":"2014","journal-title":"Virology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"29218","DOI":"10.1074\/jbc.M402576200","article-title":"Acute formation of protease-resistant prion protein does not always lead to persistent scrapie infection in vitro","volume":"279","author":"Vorberg","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"17971","DOI":"10.1073\/pnas.0708372104","article-title":"Cell division modulates prion accumulation in cultured cells","volume":"104","author":"Ghaemmaghami","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"704546","DOI":"10.1155\/2013\/704546","article-title":"Prions Ex Vivo: What Cell Culture Models Tell Us about Infectious Proteins","volume":"2013","author":"Krauss","year":"2013","journal-title":"Int. J. Cell. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"18702","DOI":"10.1074\/jbc.M701309200","article-title":"Scrapie infection of prion protein-deficient cell line upon ectopic expression of mutant prion proteins","volume":"282","author":"Maas","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"31260","DOI":"10.1074\/jbc.M109.004382","article-title":"Prion-induced activation of cholesterogenic gene expression by Srebp2 in neuronal cells","volume":"284","author":"Bach","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"16188","DOI":"10.1016\/S0021-9258(18)41985-0","article-title":"Evidence for synthesis of scrapie prion proteins in the endocytic pathway","volume":"267","author":"Borchelt","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1128\/JVI.02412-08","article-title":"Cells expressing anchorless prion protein are resistant to scrapie infection","volume":"83","author":"McNally","year":"2009","journal-title":"J. Virol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1083\/jcb.201308028","article-title":"Live imaging of prions reveals nascent PrPSc in cell-surface, raft-associated amyloid strings and webs","volume":"204","author":"Rouvinski","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1242\/jcs.165472","article-title":"The multivesicular body is the major internal site of prion conversion","volume":"128","author":"Yim","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1126\/science.7754373","article-title":"Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]","volume":"268","author":"Chernoff","year":"1995","journal-title":"Science"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/19336896.2015.1025189","article-title":"Prion aggregates transfer through tunneling nanotubes in endocytic vesicles","volume":"9","author":"Zhu","year":"2015","journal-title":"Prion"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4409","DOI":"10.1007\/s00018-015-1945-8","article-title":"Efficient inhibition of infectious prions multiplication and release by targeting the exosomal pathway","volume":"72","author":"Vilette","year":"2015","journal-title":"Cell Mol. Life Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00401-012-0944-1","article-title":"Persistent retroviral infection with MoMuLV influences neuropathological signature and phenotype of prion disease","volume":"124","author":"Krasemann","year":"2012","journal-title":"Acta Neuropathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/2909\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:33:44Z","timestamp":1760135624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/2909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,8]]},"references-count":125,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ijms23062909"],"URL":"https:\/\/doi.org\/10.3390\/ijms23062909","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,3,8]]}}}