{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:37:59Z","timestamp":1793129879404,"version":"4.5.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI195576, R01CA261258"],"award-info":[{"award-number":["R01AI195576, R01CA261258"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus implicated in inflammatory, malignant, and autoimmune diseases. Although EBV toggles between latent and lytic states, the host cues controlling this switch remain incompletely defined. Interleukin-17A (IL-17A), a signature Th17 cytokine, is enriched in EBV-associated inflammatory settings, and EBV products can augment IL-17A responses. Whether IL-17A directly regulates the EBV life cycle has remained unknown. Here, we show that IL-17A alone is sufficient to induce EBV lytic reactivation in latency I human B-cell models. IL-17A increased BZLF1\/Zta, activated the BZLF1 promoter (Zp), induced early and late lytic genes and proteins, and promoted DNase-resistant EBV DNA release and infectious virion production. Mechanistically, IL-17A activated NF-\u03baB and ERK\/p38 MAPK signaling, including phosphorylation of p65, ERK1\/2, and p38. IL-17RA blockade reduced IL-17A-induced signaling and lytic reactivation, and pharmacologic inhibition of NF-\u03baB or p38 MAPK signaling attenuated EBV reactivation. Among IL-17 family members tested, only IL-17A induced reactivation. RNA-seq provided a transcriptome-wide view of the viral and cellular response to IL-17A, revealing broad EBV lytic transcription and inflammatory, NF-\u03baB-associated, and B-cell activation programs. IL-17A responsiveness was latency- and cell-state restricted: latency I B-cell models responded, whereas latency II\/III, lymphoblastoid, and EBV-positive epithelial models did not. Subinducing IL-17A (1 ng\/mL) was insufficient alone but enhanced B-cell receptor-mediated reactivation, suggesting threshold-lowering activity in inflammatory B-cell niches. Together, these findings identify IL-17A as a receptor-linked inflammatory cue for EBV lytic entry and provide the first demonstration that IL-17A alone directly triggers EBV lytic reactivation in human cells.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Epstein-Barr virus (EBV) persists for life by maintaining latency with lytic reactivation, yet the inflammatory cues that initiate this switch remain poorly defined. Here, we identify interleukin-17A (IL-17A), a Th17 cytokine, as a direct trigger of EBV lytic reactivation in latency I human B-cell models. IL-17A activates IL-17RA-linked NF-\u03baB\/MAPK signaling, induces BZLF1\/Zta and downstream lytic genes, and promotes DNase-resistant EBV DNA release and infectious virion production. IL-17RA blockade and inhibition of NF-\u03baB\/p38 MAPK signaling reduce reactivation, supporting a receptor-linked mechanism rather than nonspecific stress. Subinducing IL-17A (1 ng\/mL) was insufficient to reactivate EBV alone but enhanced B-cell receptor-mediated reactivation, suggesting threshold-lowering activity in inflammatory B-cell niches. The response is restricted by latency and cell state, indicating that IL-17A signaling must be coupled to a permissive EBV lytic switch. These findings connect Th17-skewed inflammation to EBV reactivation burden and suggest that IL-17A\/IL-17R signaling may influence EBV pathogenesis in inflammatory and malignant settings.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00813-26","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:03:45Z","timestamp":1790255025000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Interleukin-17A directly triggers Epstein-Barr virus lytic reactivation in latency I human B-cell models"],"prefix":"10.1128","volume":"100","author":[{"given":"Janardhan","family":"Avilala","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Laboratory Medicine, Tulane University School of Medicine","place":["New Orleans, USA"]},{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Tulane Cancer Center, Tulane University School of Medicine","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotomo","family":"Dochi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Laboratory Medicine, Tulane University School of Medicine","place":["New Orleans, USA"]},{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Tulane Cancer Center, Tulane University School of Medicine","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramsy","family":"Abdelghani","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Pulmonary and Critical Care Medicine and Interventional Pulmonology, Department of Medicine, Tulane University School of Medicine","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Becnel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Pulmonary and Critical Care Medicine and Interventional Pulmonology, Department of Medicine, Tulane University School of Medicine","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Maresh","sequence":"additional","affiliation":[{"name":"Translational Cancer Research Laboratory, Ochsner Clinic Foundation","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Translational Cancer Research Laboratory, Ochsner Clinic Foundation","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Translational Cancer Research Laboratory, Ochsner Clinic Foundation","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Sides","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Tulane Cancer Center, Tulane University School of Medicine","place":["New Orleans, USA"]},{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Hematology and Medical Oncology, Department of Medicine, Tulane University School of Medicine","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Morris","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Laboratory Medicine, Tulane University School of Medicine","place":["New Orleans, USA"]},{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Tulane Cancer Center, Tulane University School of Medicine","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Tulane Cancer Center, Tulane University School of Medicine","place":["New Orleans, USA"]},{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, Tulane University School of Medicine","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9229-053X","authenticated-orcid":true,"given":"Zhen","family":"Lin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Laboratory Medicine, Tulane University School of Medicine","place":["New Orleans, USA"]},{"id":[{"id":"https:\/\/ror.org\/04vmvtb21","id-type":"ROR","asserted-by":"publisher"}],"name":"Tulane Cancer Center, Tulane University School of Medicine","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22857"},{"key":"e_1_3_4_3_2","first-page":"2655","volume-title":"Fields virology","author":"Rickinson AB","year":"2007","unstructured":"Rickinson AB, Kieff E. 2007. Epstein-Barr virus, p 2655\u20132700. In Knipe DM, Howley PM (ed), Fields virology, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"5"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.92"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11060759"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02380-13"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003341"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-023-00775-5"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8222"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01298-20"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02830-15"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00379-10"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1505191"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006404"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.16564"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.05.006"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01197-10"},{"key":"e_1_3_4_18_2","first-page":"167","volume-title":"Epstein-Barr virus: latency and transformation","author":"Lin Z","year":"2010","unstructured":"Lin Z, Flemington EK. 2010. Regulation of EBV latency by viral lytic proteins, p 167\u2013192. In Robertson ES (ed), Epstein-Barr virus: latency and transformation. Caister Academic Press, London, England."},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011939"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0514-y"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01620-3"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.367532"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.5962"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017007260"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00987-19"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2024.1243366"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.23937\/2378-3672\/1410023"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00566-21"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02517-12"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.21.11962-11971.2004"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00608-15"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt087"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024048"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194883"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/eos.13019"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224479"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.01.002"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2019.05.026"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15892-7"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6623"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20150204"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1721967115"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2013.12.008"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a003004"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019104202"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01293"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.199547"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.74.3.1224-1233.2000"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00813-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00813-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:19:17Z","timestamp":1793128757000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.00813-26"}},"subtitle":[],"editor":[{"given":"Lori","family":"Frappier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":50,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,20]]}},"alternative-id":["10.1128\/jvi.00813-26"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00813-26","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]},"assertion":[{"value":"2026-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00813-26"}}