{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T19:19:19Z","timestamp":1783451959644,"version":"3.55.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI192874"],"award-info":[{"award-number":["R01AI192874"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Program","doi-asserted-by":"publisher","award":["W81XWH-21-1-0800"],"award-info":[{"award-number":["W81XWH-21-1-0800"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dengue virus (DENV) infections cause a range of clinical symptoms, from a mild febrile illness to severe disease. Higher levels of DENV RNAemia are associated with severe dengue, although this relationship is incompletely understood. Dengue human infection models (DHIMs), in which volunteers are experimentally infected with underattenuated DENV strains, provide an invaluable tool for studying early virologic, transcriptional, and immunologic features of infection. DHIM studies using DENV-1, DENV-3, and DENV-4 have demonstrated qualitatively distinct clinical features; however, the contribution of RNAemia and serotype to divergent transcriptional and clinical profiles in these challenge models remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this work, we performed a comparative analysis of DHIM-1, DHIM-3, and DHIM-4 studies to determine shared and unique features of the transcriptional response to infection and their associations with RNAemia and clinical symptoms. We then exposed primary human peripheral blood mononuclear cells (PBMCs) in vitro to DENV-1 or DENV-3 at varying titers and performed bulk RNA sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Across DHIMs, we identified a set of conserved, upregulated genes at day of peak RNAemia, representing a core antiviral response independent of serotype. Further, a unique gene signature indicating downregulated cytoplasmic translation emerged in a subset of DHIM-3 participants with elevated RNAemia and symptomatology. In vitro PBMC exposure to DENV demonstrated that conserved and unique gene expression signatures varied as a function of viral dose rather than serotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data show that viral burden correlates with transcriptional responses and clinical symptomatology following experimental DENV infection, contributing to our understanding of dengue pathogenesis and immunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag338","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T11:50:46Z","timestamp":1782388246000},"source":"Crossref","is-referenced-by-count":0,"title":["A Comparative Analysis of the Immunotranscriptomic Features of DENV-1, -3, and -4 Human Challenge Models"],"prefix":"10.1093","author":[{"given":"C\u00e9line S C","family":"Hardy","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, State University of NewYork Upstate Medical University , Syracuse, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4145-0836","authenticated-orcid":false,"given":"Lisa A","family":"Ware","sequence":"additional","affiliation":[{"name":"Global Health Institute, State University of NewYork Upstate Medical University , Syracuse, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5173-2701","authenticated-orcid":false,"given":"Heather","family":"Friberg","sequence":"additional","affiliation":[{"name":"Viral Diseases Program, Center for Infectious Diseases Research, Walter Reed Army Institute of Research , Silver Spring, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7579-4672","authenticated-orcid":false,"given":"Joel V","family":"Chua","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4966-0830","authenticated-orcid":false,"given":"Kirsten E","family":"Lyke","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8368-7682","authenticated-orcid":false,"given":"Stephen J","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, State University of NewYork Upstate Medical University , Syracuse, New York ,","place":["USA"]},{"name":"Global Health Institute, State University of NewYork Upstate Medical University , Syracuse, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4536-6714","authenticated-orcid":false,"given":"Adam T","family":"Waickman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, State University of NewYork Upstate Medical University , Syracuse, New York ,","place":["USA"]},{"name":"Global Health Institute, State University of NewYork Upstate Medical University , Syracuse, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"2026070714163895000_jiag338-B1","volume-title":"StatPearls","author":"Schaefer","year":"2025"},{"key":"2026070714163895000_jiag338-B2","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1128\/CMR.00035-09","article-title":"Dengue virus pathogenesis: an integrated view","volume":"22","author":"Martina","year":"2009","journal-title":"Clin Microbiol Rev"},{"key":"2026070714163895000_jiag338-B3","doi-asserted-by":"crossref","first-page":"16055","DOI":"10.1038\/nrdp.2016.55","article-title":"Dengue infection","volume":"2","author":"Guzman","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"2026070714163895000_jiag338-B4","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1007\/s00705-013-1645-3","article-title":"Secondary infection as a risk factor for dengue hemorrhagic fever\/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection","volume":"158","author":"Guzman","year":"2013","journal-title":"Arch Virol"},{"key":"2026070714163895000_jiag338-B5","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1126\/science.aan6836","article-title":"Antibody-dependent enhancement of severe dengue disease in humans","volume":"358","author":"Katzelnick","year":"2017","journal-title":"Science"},{"key":"2026070714163895000_jiag338-B6","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s40249-021-00908-2","article-title":"Clinical predictors of severe dengue: a systematic review and meta-analysis","volume":"10","author":"Tsheten","year":"2021","journal-title":"Infect Dis Poverty"},{"key":"2026070714163895000_jiag338-B7","doi-asserted-by":"crossref","DOI":"10.1128\/cmr.00244-24","article-title":"Dengue and severe dengue.","volume":"38","author":"Kalimuddin","year":"2025","journal-title":"Clin Microbiol Rev"},{"key":"2026070714163895000_jiag338-B8","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1093\/infdis\/jir014","article-title":"Kinetics of plasma viremia and soluble nonstructural protein 1 concentrations in dengue: differential effects according to serotype and immune status","volume":"203","author":"Duyen","year":"2011","journal-title":"J Infect Dis"},{"key":"2026070714163895000_jiag338-B9","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1086\/382280","article-title":"Relationship of preexisting dengue virus (DV) neutralizing antibody levels to viremia and severity of disease in a prospective cohort study of DV infection in Thailand","volume":"189","author":"Endy","year":"2004","journal-title":"J Infect Dis"},{"key":"2026070714163895000_jiag338-B10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/rmv.2121","article-title":"The association between dengue viremia kinetics and dengue severity: a systemic review and meta-analysis","volume":"30","author":"Morsy","year":"2020","journal-title":"Rev Med Virol"},{"key":"2026070714163895000_jiag338-B11","doi-asserted-by":"crossref","first-page":"e1309","DOI":"10.1371\/journal.pntd.0001309","article-title":"Kinetics of viremia and NS1 antigenemia are shaped by immune status and virus serotype in adults with dengue","volume":"5","author":"Tricou","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"2026070714163895000_jiag338-B12","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1038\/s41467-021-22930-6","article-title":"Immunotranscriptomic profiling the acute and clearance phases of a human challenge dengue virus serotype 2 infection model","volume":"12","author":"Hanley","year":"2021","journal-title":"Nat Commun"},{"key":"2026070714163895000_jiag338-B13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1086\/315215","article-title":"Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity","volume":"181","author":"Vaughn","year":"2000","journal-title":"J Infect Dis"},{"key":"2026070714163895000_jiag338-B14","doi-asserted-by":"crossref","first-page":"e1074","DOI":"10.1093\/cid\/ciaa1840","article-title":"Higher plasma viremia in the febrile phase is associated with adverse dengue outcomes irrespective of infecting serotype or host immune status: an analysis of 5642 Vietnamese cases","volume":"72","author":"Vuong","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2026070714163895000_jiag338-B15","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/s41467-019-09193-y","article-title":"Effects of infection history on dengue virus infection and pathogenicity","volume":"10","author":"Tsang","year":"2019","journal-title":"Nat Commun"},{"issue":"Suppl 2","key":"2026070714163895000_jiag338-B16","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1093\/infdis\/jiu061","article-title":"Dengue human infection model: introduction","volume":"209","author":"Cassetti","year":"2014","journal-title":"J Infect Dis"},{"key":"2026070714163895000_jiag338-B17","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/infdis\/jiaa351","article-title":"A phase 1, open-label assessment of a dengue virus-1 live virus human challenge strain","volume":"223","author":"Endy","year":"2021","journal-title":"J Infect Dis"},{"key":"2026070714163895000_jiag338-B18","doi-asserted-by":"crossref","first-page":"eabo5019","DOI":"10.1126\/scitranslmed.abo5019","article-title":"Evolution of inflammation and immunity in a dengue virus 1 human infection model","volume":"14","author":"Waickman","year":"2022","journal-title":"Sci Transl Med"},{"key":"2026070714163895000_jiag338-B19","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1038\/s41564-024-01668-z","article-title":"Low-dose dengue virus 3 human challenge model: a phase 1 open-label study","volume":"9","author":"Waickman","year":"2024","journal-title":"Nat Microbiol"},{"key":"2026070714163895000_jiag338-B20","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S1473-3099(24)00100-2","article-title":"Efficacy and immunogenicity following dengue virus-1 human challenge after a tetravalent prime-boost dengue vaccine regimen: an open-label, phase 1 trial","volume":"24","author":"Lyke","year":"2024","journal-title":"Lancet Infect Dis"},{"key":"2026070714163895000_jiag338-B21","author":"Chua"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiag338\/68630183\/jiag338.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiag338\/68630183\/jiag338.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:16:46Z","timestamp":1783448206000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/advance-article\/doi\/10.1093\/infdis\/jiag338\/8719301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,27]]},"references-count":21,"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiag338","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,27]]},"article-number":"jiag338"}}