{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T22:32:13Z","timestamp":1784932333019,"version":"3.55.0"},"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S01411X\/1"],"award-info":[{"award-number":["MR\/S01411X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022850","name":"Little Princess Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008634","name":"Neuroblastoma UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008634","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008176","name":"Wessex Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008176","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Despite decades of research, survival from brain cancer has scarcely improved and is drastically lower than that of other cancers. Novel therapies, such as immunotherapy, hold great promise for treating brain tumours and are desperately needed. Zika virus (ZIKV) infects and kills aggressive cancer cells with stem-like properties (CSCs) from both paediatric and adult brain tumours. Whilst T cell recruitment into ZIKV-infected brain tumours is becoming well documented, the specific mechanisms through which they are activated are poorly understood. We address this by employing a combined global proteome and immunopeptidome mass spectrometry approach to describe, for the first time, human leukocyte antigen (HLA) presentation of ZIKV peptides on the surface of infected brain tumour cells. We first show that antigen processing and presentation by HLA class I (HLA-I) is the top enriched immune response pathway in the global proteome of aggressive paediatric USP7-ATRT brain tumour cells following ZIKV infection. We identify USP7-ATRT cells as a desirable immunopeptidome model as they express the globally common HLA-A allotype (A*02:01). We predict the majority of our 19 identified ZIKV peptides to strongly bind and be presented by HLA-A*02:01. We observe a trend between immunopeptide presentation and cellular ZIKV protein abundance, with nearly half of the peptides arising from the most abundant viral protein; non-structural protein 3 (NS3). We show the ZIKV NS3 helicase domain to be a particularly rich source of peptides. Finally, we verify that the 19 ZIKV peptides identified here are not predicted to mimic peptides of the human proteome. The ZIKV peptides we identify here are novel targets for immunotherapy, and our findings provide potential insight into the efficacious cytotoxic T cell response that oncolytic ZIKV virotherapy can induce against brain tumours.<\/jats:p>","DOI":"10.1371\/journal.pone.0335726","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:31:17Z","timestamp":1761845477000},"page":"e0335726","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of natural Zika virus peptides presented on the surface of paediatric brain tumour cells by HLA class I"],"prefix":"10.1371","volume":"20","author":[{"given":"Matt","family":"Sherwood","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Nicholas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0023-8679","authenticated-orcid":true,"given":"Alistair","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Giove","family":"Mitsugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolini","family":"Kaid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oswaldo K.","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Skipp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-4001","authenticated-orcid":true,"given":"Rob M.","family":"Ewing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"issue":"6","key":"pone.0335726.ref001","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/tan.13811","article-title":"Common, intermediate and well-documented HLA alleles in world populations: CIWD version 3.0.0","volume":"95","author":"CK Hurley","year":"2020","journal-title":"HLA"},{"key":"pone.0335726.ref002","doi-asserted-by":"crossref","DOI":"10.1093\/neuonc\/noac202","article-title":"CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015\u20132019","volume":"24","author":"QT Ostrom","year":"2022","journal-title":"Neuro-Oncology"},{"key":"pone.0335726.ref003","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jare.2022.06.001","article-title":"Global, regional, and national childhood cancer burden, 1990\u20132019: An analysis based on the Global Burden of Disease Study 2019","volume":"40","author":"Y Wu","year":"2022","journal-title":"J Adv Res"},{"key":"pone.0335726.ref004","article-title":"Editorial: Cancer cell-intrinsic and -extrinsic factors affecting tumor immune evasion","volume":"14","author":"J Sun","year":"2023","journal-title":"Front Immunol"},{"issue":"5","key":"pone.0335726.ref005","first-page":"465","article-title":"Introduction to immunotherapy for brain tumor patients: challenges and future perspectives","volume":"7","author":"ML Montoya","year":"2020","journal-title":"Neurooncol Pract"},{"key":"pone.0335726.ref006","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s12935-022-02585-z","article-title":"Biological causes of immunogenic cancer cell death (ICD) and anti-tumor therapy; combination of oncolytic virus-based immunotherapy and CAR T-cell therapy for ICD induction","volume":"22","author":"A Mardi","year":"2022","journal-title":"Cancer Cell Int"},{"issue":"7","key":"pone.0335726.ref007","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/nbt.2287","article-title":"Oncolytic virotherapy","volume":"30","author":"SJ Russell","year":"2012","journal-title":"Nat Biotechnol"},{"issue":"20","key":"pone.0335726.ref008","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21207505","article-title":"Clinical application of oncolytic viruses: a systematic review","volume":"21","author":"M Cook","year":"2020","journal-title":"Int J Mol Sci"},{"key":"pone.0335726.ref009","unstructured":"ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/. 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