{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:26:38Z","timestamp":1792265198140,"version":"4.4.0"},"reference-count":84,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"European Union \u2013 Next Generation EU under the National Recovery and Resilience Plan","award":["2022-PNRR-P2022ALFEK"],"award-info":[{"award-number":["2022-PNRR-P2022ALFEK"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,7,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Alpha-synuclein (\u03b1-syn) is best known as a presynaptic protein that supports synaptic vesicle dynamics and neurotransmission. Conversely, misfolded or aggregated \u03b1-syn represents a hallmark of synucleinopathies, including Parkinson\u2019s disease. Beyond the nervous system, \u03b1-syn has been detected in peripheral compartments, including blood cells and selected epithelial tissues, although the robustness and context dependence of expression outside neuronal and erythroid lineages remain under active investigation. Also, it can be released extracellularly through unconventional secretion or cell damage. These observations have reframed \u03b1-syn as an immune-relevant molecule positioned at host\u2013pathogen interfaces, endowed with antimicrobial peptide-like and damage-associated molecular pattern-like properties that enable shaping of both innate and adaptive immunity. Increasing evidence indicates that viral challenge alters \u03b1-syn expression, localization, and conformational states in central and peripheral settings, in part through interferon-dependent programs that couple antiviral immunity with cellular homeostasis. A plethora of RNA viruses, such as influenza virus, flavivirus, enterovirus, and coronavirus, perturb \u03b1-syn abundance, post-translational modifications, trafficking, secretion, and aggregation propensity. These effects converge on shared mechanisms that include altered proteostasis, autophagy\u2013lysosomal dysfunction, oxidative and mitochondrial injury, and inflammatory signaling. Importantly, outcomes are highly context dependent, ranging from cell-intrinsic antiviral restriction to aggregation-prone states that may fuel chronic inflammation and neurodegeneration. Collectively, the evidence discussed herein supports a dual framework in which \u03b1-syn contributes to antiviral defense; yet, under conditions of sustained inflammation or impaired clearance, it may undergo pathological transformation that promotes neuronal damage. Defining when virus-induced \u03b1-syn responses are protective versus pathogenic, and clarifying their relevance to human disease, will be critical for developing strategies that target host\u2013virus interactions, neuroinflammation, and \u03b1-syn proteostasis in infection-associated synucleinopathies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00191-26","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T13:05:31Z","timestamp":1781010331000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Alpha-synuclein at the crossroads of host\u2013virus interactions: immunological roles beyond the nervous system"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4267-2596","authenticated-orcid":true,"given":"Valentina","family":"Artusa","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical and Clinical Sciences, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0185-2099","authenticated-orcid":true,"given":"Fiona","family":"Limanaqi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical and Clinical Sciences, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Santacroce","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02d4c4y02","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia","place":["Modena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5920-6191","authenticated-orcid":true,"given":"Mario","family":"Clerici","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathophysiology and Transplantation, University of Milan","place":["Milan, Italy"]},{"name":"IRCCS Fondazione Don Carlo Gnocchi ONLUS","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cossarizza","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02d4c4y02","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia","place":["Modena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3671-4235","authenticated-orcid":true,"given":"Mara","family":"Biasin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical and Clinical Sciences, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4268-6552","authenticated-orcid":true,"given":"Lara","family":"Gibellini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02d4c4y02","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia","place":["Modena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9535-3359","authenticated-orcid":true,"given":"Daria","family":"Trabattoni","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical and Clinical Sciences, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-150642"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13570"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2024.105760"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.07.018"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.4081\/ejh.2021.3310"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7228"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2019.e02590"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10059-000-0065-x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105654"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2011.00080"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06695.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2534"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature22815"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-023-00482-x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1906466117"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-41240-z"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02949-15"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00418-24"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-025-03639-2"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-025-05985-2"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1421360"},{"key":"e_1_3_3_23_2","volume-title":"Madame Curie Bioscience Database 2000-2013","author":"Yang ML","year":"2000","unstructured":"Yang ML, Julia MG. 2000. \u03b1-Synuclein Physiology and Membrane Binding. In Madame Curie Bioscience Database 2000-2013. Landes Bioscience."},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.08.052"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.769506"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2019.06.002"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2023.578047"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2011.09.008"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0133863"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110090"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2005965"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22437"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001376"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-140491"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nly024"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2013.01.004"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32625-1"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010018"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900096106"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-019-0090-8"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac192"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007617"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00046"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2021.113845"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101570"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12061223"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23063394"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2025.05.021"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amsu.2022.104281"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30305-7"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22137135"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.irn.2022.04.004"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0329-1"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01239-7"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.1c00666"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03726-9"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.03.100"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c03925"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.3c00468"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-73535-0"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000239"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.189988"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.457408"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1915641"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-017-1682-2"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56099-z"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1080\/13550280802578075"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2024.110141"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1159\/000479653"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1159\/000477990"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00946"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5123-11.2012"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70062-6"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053462"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam9080"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05865"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5311-12.2013"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-017-2541-x"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06251-8"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28774"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01113-x"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac270"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-017-0452-6"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252212079"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.5c00478"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00191-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00191-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:05:24Z","timestamp":1784639124000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.00191-26"}},"subtitle":[],"editor":[{"given":"Herman W.","family":"Favoreel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":84,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7,21]]}},"alternative-id":["10.1128\/jvi.00191-26"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00191-26","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]},"assertion":[{"value":"2026-06-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00191-26"}}