{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:19:10Z","timestamp":1793035150899,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013432","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000}}],"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jardine Foundation"},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["222426\/Z\/21\/Z"],"award-info":[{"award-number":["222426\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["U19 I082360"],"award-info":[{"award-number":["U19 I082360"]}]},{"name":"University of Oxford NDM COVID-19 emergency relief fund"},{"name":"Pandemic Sciences Institute"},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["227217\/Z\/23\/Z"],"award-info":[{"award-number":["227217\/Z\/23\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/Y004450\/1"],"award-info":[{"award-number":["MR\/Y004450\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The COVID-19 pandemic response demonstrated the effectiveness of adenovirus vector vaccines in inducing protective cellular and antibody responses. However, we still lack mechanistic understanding of the factors regulating immunity induced by this platform, especially innate pathways. We utilized a human tonsil organoid model to study the regulation of adaptive responses to ChAdOx1 nCoV-19. Innate activation and cytokine release occurred within 24 hours and T and B cell activation and antigen-specific antibody secretion occurred during the ensuing 14-day culture. Among the immune cell populations, plasmacytoid dendritic cells (pDCs) exhibited the highest ChAdOx1 transduction levels. pDC-derived IFN-\u0251 was critical for humoral responses, but production of antigen in pDCs was dispensable. Furthermore, IL-6 enhanced humoral responses in both IFN-\u0251-dependent and independent manners, indicating intricate signaling interplay. IFN-\u0251 and IL-6 also regulated the function of vaccine-activated CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, including T\n                    <jats:sub>FH<\/jats:sub>\n                    . These data provide key insights into innate pathways regulating ChAdOx1-induced immunity and highlights the promise of this model for vaccine platform mechanistic studies.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013432","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T17:51:32Z","timestamp":1755885092000},"page":"e1013432","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Human tonsil organoids reveal innate pathways modulating humoral and cellular responses to ChAdOx1"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6367-5046","authenticated-orcid":true,"given":"Maria Fransiska","family":"Pudjohartono","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1826-953X","authenticated-orcid":true,"given":"Kate","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0860-0831","authenticated-orcid":true,"given":"Eleanor","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4307-9161","authenticated-orcid":true,"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9694-2216","authenticated-orcid":true,"given":"Nicholas M.","family":"Provine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"issue":"10269","key":"ppat.1013432.ref001","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0140-6736(20)32661-1","article-title":"Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK","volume":"397","author":"M Voysey","year":"2021","journal-title":"Lancet"},{"issue":"10321","key":"ppat.1013432.ref002","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0140-6736(21)02753-7","article-title":"Final efficacy analysis, interim safety analysis, and immunogenicity of a single dose of recombinant novel coronavirus vaccine (adenovirus type 5 vector) in adults 18 years and older: an international, multicentre, randomised, double-blinded, placebo-controlled phase 3 trial","volume":"399","author":"SA Halperin","year":"2022","journal-title":"Lancet"},{"issue":"9","key":"ppat.1013432.ref003","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1056\/NEJMoa2117608","article-title":"Final analysis of efficacy and safety of single-dose Ad26.COV2.S","volume":"386","author":"J Sadoff","year":"2022","journal-title":"N Engl J Med"},{"issue":"6","key":"ppat.1013432.ref004","doi-asserted-by":"crossref","DOI":"10.1002\/eji.202250022","article-title":"Adenovirus vector and mRNA vaccines: mechanisms regulating their immunogenicity","volume":"53","author":"NM Provine","year":"2023","journal-title":"Eur J Immunol"},{"issue":"12","key":"ppat.1013432.ref005","doi-asserted-by":"crossref","first-page":"100845","DOI":"10.1016\/j.xcrm.2022.100845","article-title":"Tfh cells and the germinal center are required for memory B cell formation & humoral immunity after ChAdOx1 nCoV-19 vaccination","volume":"3","author":"WS Foster","year":"2022","journal-title":"Cell Rep Med"},{"issue":"1","key":"ppat.1013432.ref006","doi-asserted-by":"crossref","DOI":"10.1002\/eji.202451142","article-title":"Distinct requirements for CD4+ T cell help for immune responses induced by mRNA and adenovirus-vector SARS-CoV-2 vaccines","volume":"55","author":"L Yong","year":"2025","journal-title":"Eur J Immunol"},{"issue":"9","key":"ppat.1013432.ref007","doi-asserted-by":"crossref","first-page":"4278","DOI":"10.1128\/JVI.00039-16","article-title":"Transient CD4+ T cell depletion results in delayed development of functional vaccine-elicited antibody responses","volume":"90","author":"NM Provine","year":"2016","journal-title":"J Virol"},{"issue":"12","key":"ppat.1013432.ref008","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1038\/s41590-022-01329-5","article-title":"Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination","volume":"23","author":"S Fourati","year":"2022","journal-title":"Nat Immunol"},{"issue":"12","key":"ppat.1013432.ref009","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1038\/s41590-022-01328-6","article-title":"Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses","volume":"23","author":"T Hagan","year":"2022","journal-title":"Nat Immunol"},{"issue":"2","key":"ppat.1013432.ref010","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/imm.12957","article-title":"Toll-like receptor 4 signalling regulates antibody response to adenoviral vector-based vaccines by imprinting germinal centre quality","volume":"155","author":"R Li","year":"2018","journal-title":"Immunology"},{"issue":"6","key":"ppat.1013432.ref011","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.4049\/jimmunol.178.6.3505","article-title":"Type I IFN signaling on both B and CD4 T cells is required for protective antibody response to adenovirus","volume":"178","author":"J Zhu","year":"2007","journal-title":"J Immunol"},{"issue":"638","key":"ppat.1013432.ref012","article-title":"A homologous or variant booster vaccine after Ad26.COV2.S immunization enhances SARS-CoV-2-specific immune responses in rhesus macaques","volume":"14","author":"X He","year":"2022","journal-title":"Sci Transl Med"},{"issue":"1","key":"ppat.1013432.ref013","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41591-020-01145-0","article-title":"Modeling human adaptive immune responses with tonsil organoids","volume":"27","author":"LE Wagar","year":"2021","journal-title":"Nat Med"},{"issue":"8","key":"ppat.1013432.ref014","doi-asserted-by":"crossref","DOI":"10.1016\/j.immuni.2023.06.019","article-title":"Influenza vaccine format mediates distinct cellular and antibody responses in human immune organoids","volume":"56","author":"JM Kastenschmidt","year":"2023","journal-title":"Immunity"},{"issue":"3","key":"ppat.1013432.ref015","first-page":"380","article-title":"A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2","volume":"22","author":"Q Yin","year":"2023","journal-title":"Nat Mater"},{"key":"ppat.1013432.ref016","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1373537","article-title":"Tissue-specific sex differences in pediatric and adult immune cell composition and function","volume":"15","author":"MT Mitul","year":"2024","journal-title":"Front Immunol"},{"issue":"12","key":"ppat.1013432.ref017","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.4049\/jimmunol.2100063","article-title":"Defining T cell subsets in human tonsils using ChipCytometry","volume":"206","author":"JP Hagel","year":"2021","journal-title":"J Immunol"},{"issue":"7875","key":"ppat.1013432.ref018","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41586-021-03841-4","article-title":"Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine","volume":"597","author":"V Oberhardt","year":"2021","journal-title":"Nature"},{"issue":"2","key":"ppat.1013432.ref019","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/0165-5876(95)01298-2","article-title":"Spontaneous immunoglobulin production by adenoidal and tonsillar lymphocytes in relation to age and otitis media with effusion","volume":"35","author":"Y Harabuchi","year":"1996","journal-title":"Int J Pediatr Otorhinolaryngol"},{"issue":"5","key":"ppat.1013432.ref020","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.immuni.2017.04.009","article-title":"Metabolic regulation of the immune humoral response","volume":"46","author":"M Boothby","year":"2017","journal-title":"Immunity"},{"issue":"66","key":"ppat.1013432.ref021","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abl5842","article-title":"Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses","volume":"6","author":"J Feldman","year":"2021","journal-title":"Sci Immunol"},{"key":"ppat.1013432.ref022","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.3389\/fimmu.2019.02458","article-title":"Challenges and opportunities for consistent classification of human B cell and plasma cell populations","volume":"10","author":"I Sanz","year":"2019","journal-title":"Front Immunol"},{"issue":"7","key":"ppat.1013432.ref023","doi-asserted-by":"crossref","first-page":"4034","DOI":"10.4049\/jimmunol.174.7.4034","article-title":"Increased expression of CD27 on activated human memory B cells correlates with their commitment to the plasma cell lineage","volume":"174","author":"DT Avery","year":"2005","journal-title":"J Immunol"},{"issue":"6528","key":"ppat.1013432.ref024","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1126\/science.aax8819","article-title":"MAIT cell activation augments adenovirus vector vaccine immunogenicity","volume":"371","author":"NM Provine","year":"2021","journal-title":"Science"},{"issue":"26","key":"ppat.1013432.ref025","doi-asserted-by":"crossref","first-page":"3813","DOI":"10.1016\/j.vaccine.2023.04.049","article-title":"COVID-19 adenovirus vector vaccine induces higher interferon and pro-inflammatory responses than mRNA vaccines in human PBMCs, macrophages and moDCs","volume":"41","author":"M Jiang","year":"2023","journal-title":"Vaccine"},{"issue":"18","key":"ppat.1013432.ref026","doi-asserted-by":"crossref","first-page":"9590","DOI":"10.1128\/JVI.00740-12","article-title":"Vaccination with adenovirus serotypes 35, 26, and 48 elicits higher levels of innate cytokine responses than adenovirus serotype 5 in rhesus monkeys","volume":"86","author":"JE Teigler","year":"2012","journal-title":"J Virol"},{"issue":"2","key":"ppat.1013432.ref027","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.cyto.2015.02.007","article-title":"B cells responses and cytokine production are regulated by their immune microenvironment","volume":"74","author":"MI Vazquez","year":"2015","journal-title":"Cytokine"},{"issue":"6","key":"ppat.1013432.ref028","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1182\/blood.V97.6.1817","article-title":"Interleukin-6 is a growth factor for nonmalignant human plasmablasts","volume":"97","author":"G Jego","year":"2001","journal-title":"Blood"},{"issue":"10","key":"ppat.1013432.ref029","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1002\/eji.1830171004","article-title":"Production of hybridoma growth factor by human monocytes","volume":"17","author":"LA Aarden","year":"1987","journal-title":"Eur J Immunol"},{"issue":"4","key":"ppat.1013432.ref030","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.immuni.2014.10.004","article-title":"T follicular helper cell differentiation, function, and roles in disease","volume":"41","author":"S Crotty","year":"2014","journal-title":"Immunity"},{"key":"ppat.1013432.ref031","doi-asserted-by":"crossref","first-page":"155654","DOI":"10.1016\/j.cyto.2021.155654","article-title":"Role of IL-6 in the commitment of T cell subsets","volume":"146","author":"T Korn","year":"2021","journal-title":"Cytokine"},{"key":"ppat.1013432.ref032","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev-immunol-120419-022408","article-title":"Germinal centers","volume":"40","author":"GD Victora","year":"2022","journal-title":"Annu Rev Immunol"},{"issue":"3","key":"ppat.1013432.ref033","doi-asserted-by":"crossref","first-page":"100971","DOI":"10.1016\/j.xcrm.2023.100971","article-title":"A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA and adenovirus vectored vaccines","volume":"4","author":"FJ Ryan","year":"2023","journal-title":"Cell Rep Med"},{"issue":"6","key":"ppat.1013432.ref034","article-title":"IFN-\u03b1 as an adjuvant for adenovirus-vectored FMDV subunit vaccine through improving the generation of T follicular helper cells","volume":"8","author":"C Su","year":"2013","journal-title":"PLoS One"},{"key":"ppat.1013432.ref035","doi-asserted-by":"crossref","first-page":"701","DOI":"10.3389\/fimmu.2020.00701","article-title":"1IFN-\u03b1 modulates memory Tfh cells and memory B cells in mice, following recombinant FMDV adenoviral challenge","volume":"11","author":"X Duan","year":"2020","journal-title":"Front Immunol"},{"issue":"7","key":"ppat.1013432.ref036","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.4049\/jimmunol.174.7.4043","article-title":"Plasmacytoid dendritic cells control TLR7 sensitivity of naive B cells via type I IFN","volume":"174","author":"IB Bekeredjian-Ding","year":"2005","journal-title":"J Immunol"},{"issue":"4","key":"ppat.1013432.ref037","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41423-018-0010-6","article-title":"Type I interferons promote the survival and proinflammatory properties of transitional B cells in systemic lupus erythematosus patients","volume":"16","author":"M Liu","year":"2019","journal-title":"Cell Mol Immunol"},{"issue":"2","key":"ppat.1013432.ref038","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S1074-7613(03)00208-5","article-title":"Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6","volume":"19","author":"G Jego","year":"2003","journal-title":"Immunity"},{"key":"ppat.1013432.ref039","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.antiviral.2016.05.021","article-title":"A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA","volume":"132","author":"AN Aljurayyan","year":"2016","journal-title":"Antiviral Res"},{"issue":"22","key":"ppat.1013432.ref040","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00925-21","article-title":"Type I interferon promotes humoral immunity in viral vector vaccination","volume":"95","author":"C Zhong","year":"2021","journal-title":"J Virol"},{"issue":"6","key":"ppat.1013432.ref041","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1182\/blood-2005-07-2709","article-title":"Specialization, kinetics, and repertoire of type 1 interferon responses by human plasmacytoid predendritic cells","volume":"107","author":"T Ito","year":"2006","journal-title":"Blood"},{"key":"ppat.1013432.ref042","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.bbi.2015.04.009","article-title":"Interdependent and independent roles of type I interferons and IL-6 in innate immune, neuroinflammatory and sickness behaviour responses to systemic poly I:C","volume":"48","author":"C Murray","year":"2015","journal-title":"Brain Behav Immun"},{"issue":"7","key":"ppat.1013432.ref043","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrrheum.2017.83","article-title":"The role of IL-6 in host defence against infections: immunobiology and clinical implications","volume":"13","author":"S Rose-John","year":"2017","journal-title":"Nat Rev Rheumatol"},{"key":"ppat.1013432.ref044","doi-asserted-by":"crossref","first-page":"1049157","DOI":"10.3389\/fmed.2023.1049157","article-title":"The accelerated waning of immunity and reduced effect of booster in patients treated with bDMARD and tsDMARD after SARS-CoV-2 mRNA vaccination","volume":"10","author":"S Tobudic","year":"2023","journal-title":"Front Med (Lausanne)"},{"issue":"5","key":"ppat.1013432.ref045","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1136\/ard-2023-225162","article-title":"Immunomodulators and risk for breakthrough COVID-19 after third SARS-CoV-2 mRNA vaccine among patients with rheumatoid arthritis: a cohort study","volume":"83","author":"AE Schiff","year":"2024","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"ppat.1013432.ref046","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.4049\/jimmunol.1300675","article-title":"Type I IFN induces binding of STAT1 to Bcl6: divergent roles of STAT family transcription factors in the T follicular helper cell genetic program","volume":"192","author":"S Nakayamada","year":"2014","journal-title":"J Immunol"},{"issue":"6057","key":"ppat.1013432.ref047","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1126\/science.1208421","article-title":"Late interleukin-6 escalates T follicular helper cell responses and controls a chronic viral infection","volume":"334","author":"JA Harker","year":"2011","journal-title":"Science"},{"key":"ppat.1013432.ref048","doi-asserted-by":"crossref","first-page":"932388","DOI":"10.3389\/fimmu.2022.932388","article-title":"Type I interferons promote germinal centers through B cell intrinsic signaling and dendritic cell dependent Th1 and Tfh cell lineages","volume":"13","author":"MW Dahlgren","year":"2022","journal-title":"Front Immunol"},{"issue":"8","key":"ppat.1013432.ref049","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1073\/pnas.1610630114","article-title":"A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes","volume":"114","author":"H Zhang","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ppat.1013432.ref050","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41590-017-0012-z","article-title":"Diversification of human plasmacytoid predendritic cells in response to a single stimulus","volume":"19","author":"SG Alculumbre","year":"2018","journal-title":"Nat Immunol"},{"issue":"24","key":"ppat.1013432.ref051","doi-asserted-by":"crossref","first-page":"3184","DOI":"10.1182\/blood-2016-11-751040","article-title":"Plasmacytoid and conventional dendritic cells cooperate in crosspriming AAV capsid-specific CD8+ T cells","volume":"129","author":"GL Rogers","year":"2017","journal-title":"Blood"},{"issue":"38","key":"ppat.1013432.ref052","doi-asserted-by":"crossref","first-page":"23730","DOI":"10.1073\/pnas.2002345117","article-title":"Plasmacytoid dendritic cells cross-prime naive CD8 T cells by transferring antigen to conventional dendritic cells through exosomes","volume":"117","author":"C Fu","year":"2020","journal-title":"Proc Natl Acad Sci U S A"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1013432","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013432","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T17:48:08Z","timestamp":1756403288000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013432"}},"subtitle":[],"editor":[{"given":"Rahul","family":"Suryawanshi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,22]]},"references-count":52,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1013432","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.10.11.617829","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,22]]}}}