{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:41:12Z","timestamp":1753882872229,"version":"3.41.2"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["21K07462"],"award-info":[{"award-number":["21K07462"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Joint Usage and Joint Research Programs, the Institute for Advanced Medical Sciences, Tokushima University"},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["23K27489"],"award-info":[{"award-number":["23K27489"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,9,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Production of the amyloidogenic prion protein, PrP\n              <jats:sup>Sc<\/jats:sup>\n              , which forms infectious protein aggregates, or prions, is a key pathogenic event in prion diseases. Functional prion-like protein aggregations, such as the mitochondrial adaptor protein MAVS and the inflammasome component protein ASC, have been identified to play a protective role in viral infections in mammalian cells. In this study, to investigate if PrP\n              <jats:sup>Sc<\/jats:sup>\n              could play a functional role against external stimuli, we infected prion-infected cells with a neurotropic influenza A virus strain, IAV\/WSN. We found that prion-infected cells were highly resistant to IAV\/WSN infection. In these cells, NF-\u03baB nuclear translocation was disturbed; therefore, mitochondrial superoxide dismutase (mtSOD) expression was suppressed, and mitochondrial reactive oxygen species (mtROS) was increased. The elevated mtROS subsequently activated NLRP3 inflammasomes, leading to the suppression of IAV\/WSN-induced necroptosis. We also found that prion-infected cells accumulated a portion of PrP molecules in the cytosol, and that the N-terminal potential nuclear translocation signal of PrP impeded NF-\u03baB nuclear translocation. These results suggest that PrP\n              <jats:sup>Sc<\/jats:sup>\n              might play a functional role in protection against viral infections by stimulating the NLRP3 inflammasome-dependent antivirus mechanism through the cytosolic PrP-mediated disturbance of NF-\u03baB nuclear translocation, which leads to suppression of mtSOD expression and consequently upregulation of the NLRP3 inflammasome activator mtROS.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>Cytosolic PrP has been detected in prion-infected cells and suggested to be involved in the neurotoxicity of prions. Here, we also detected cytosolic PrP in prion-infected cells. We further found that the nuclear translocation of NF-\u03baB was disturbed in prion-infected cells and that the N-terminal potential nuclear translocation signal of PrP expressed in the cytosol disturbed the nuclear translocation of NF-\u03baB. Thus, the N-terminal nuclear translocation signal of cytosolic PrP might play a role in prion neurotoxicity. Prion-like protein aggregates in other protein misfolding disorders, including Alzheimer's disease were reported to play a protective role against various environmental stimuli. We here showed that prion-infected cells were partially resistant to IAV\/WSN infection due to the cytosolic PrP-mediated disturbance of the nuclear translocation of NF-\u03baB, which consequently activated NLRP3 inflammasomes after IAV\/WSN infection. It is thus possible that prions could also play a protective role in viral infections.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01262-24","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T13:01:04Z","timestamp":1724850064000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Protective role of cytosolic prion protein against virus infection in prion-infected cells"],"prefix":"10.1128","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8455-5060","authenticated-orcid":false,"given":"Hideyuki","family":"Hara","sequence":"first","affiliation":[{"name":"Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University","place":["Tokushima, Japan"]},{"name":"Core Research Facility, Center for Infectious Disease Education and Research (CiDER), Osaka University","place":["Osaka, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junji","family":"Chida","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University","place":["Tokushima, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Batzaya","family":"Batchuluun","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University","place":["Tokushima, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etsuhisa","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Enzyme Chemistry, The Institute for Enzyme Research, Tokushima University (KOSOKEN)","place":["Tokushima, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Kido","sequence":"additional","affiliation":[{"name":"Division of Enzyme Chemistry, The Institute for Enzyme Research, Tokushima University (KOSOKEN)","place":["Tokushima, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8824-3124","authenticated-orcid":true,"given":"Suehiro","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University","place":["Tokushima, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1998.tb00171.x"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature20415"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102181"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-022-03676-z"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13363"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90360-3"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.22.10608"},{"key":"e_1_3_5_9_2","first-page":"331","article-title":"PrP gene dosage determines the timing but not the final intensity or distribution of lesions in scrapie pathology","volume":"3","author":"Manson JC","year":"1994","unstructured":"Manson JC, Clarke AR, McBride PA, McConnell I, Hope J. 1994. PrP gene dosage determines the timing but not the final intensity or distribution of lesions in scrapie pathology. Neurodegeneration 3:331\u2013340.","journal-title":"Neurodegeneration"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.69.12.7586-7592.1995"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21134742"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.adgen.2020.01.002"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)80231-7"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/35040758"},{"key":"e_1_3_5_15_2","first-page":"347","article-title":"A cytoplasmically inherited prionlike genetic element in yeast","volume":"1","author":"Lindquist S","year":"1996","unstructured":"Lindquist S. 1996. A cytoplasmically inherited prionlike genetic element in yeast. Mol Psychiatry 1:347\u2013348.","journal-title":"Mol Psychiatry"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(96)10045-7"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2018.07.017"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0923-2508(01)01239-6"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.56.013002.100603"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10875"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1191081"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1219491"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.18.9773"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2011.02.019"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1102762108"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2019.11.012"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.06.041"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2020.10.001"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114316"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-011-9696-z"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50435-5"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2873"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09663"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.3.639.639"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.04.001"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0969-9961(02)00014-1"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00396-18"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-18-07183.2003"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.21775\/9781912530076.05"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28846-z"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.19.5383"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.011578098"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2008.06.011"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.006186"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010465"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/45574"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5352.827"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.03.042"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00950.x"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03761-6"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010670"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2007.09.077"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900096106"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.3109\/13550289709015803"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.3109\/17482960903262083"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1023\/a:1023067728557"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-89586-6"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.06.030"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007049"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900604106"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.01262-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.01262-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T14:27:34Z","timestamp":1742394454000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.01262-24"}},"subtitle":[],"editor":[{"given":"Stacey","family":"Schultz-Cherry","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,9,17]]},"references-count":59,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9,17]]}},"alternative-id":["10.1128\/jvi.01262-24"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01262-24","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"type":"print","value":"0022-538X"},{"type":"electronic","value":"1098-5514"}],"subject":[],"published":{"date-parts":[[2024,9,17]]},"assertion":[{"value":"2024-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01262-24"}}