{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:21:55Z","timestamp":1790709715230,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"1","funder":[{"name":"Military Infectious Disease Research Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dengue virus (DENV) is an arboviral pathogen found in &amp;gt;100 countries and a source of significant morbidity and mortality. While the mechanisms underpinning the pathophysiology of severe Dengue are incompletely understood, it has been hypothesized that antibodies directed against the DENV envelope (E) protein can facilitate antibody-dependent enhancement (ADE) of the infection, increasing the number of infected cells and the severity of disease in an exposed individual. Accordingly, there is interest in defining mechanisms for directly targeting DENV-infected cells for immunologic clearance, an approach that bypasses the risk of ADE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We have previously demonstrated that antibodies specific to DENV nonstructural protein 1 (NS1) can opsonize and facilitate the phagocytic clearance of DENV-infected cells. However, it is currently unclear if other DENV antigens are expressed on the surface of infected cells and if these antigens can be targeted by antibody-dependent clearance mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this study, we demonstrate that DENV structural proteins are expressed on the surface of DENV-infected cells and that these antigens can be opsonized by both DENV-immune sera and monoclonal antibodies. In addition, DENV E\u2013specific antibodies can facilitate phagocytic uptake of material from DENV-infected cells, resulting in the target\u2013cell membrane localizing to endosomes of the engulfing phagocyte. Notably, there was no selective enrichment of DENV genomic material in monocytes that had phagocytosed DENV-infected cell material compared with nonphagocytic monocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In their totality, these data reinforce the concept that DENV E\u2013reactive antibodies have a multifaceted role in DENV immunity and pathogenesis beyond neutralization and\/or infection enhancement.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofae720","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T16:34:27Z","timestamp":1733848467000},"source":"Crossref","is-referenced-by-count":8,"title":["Dengue Virus Structural Proteins Are Expressed on the Surface of DENV-Infected Cells and Are a Target for Antibody-Dependent Cellular Phagocytosis"],"prefix":"10.1093","volume":"12","author":[{"given":"Mitchell J","family":"Waldran","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, State University of New York Upstate Medical University , Syracuse, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A","family":"Kurtz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, State University of New York Upstate Medical University , Syracuse, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad J","family":"Gebo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, State University of New York Upstate Medical University , Syracuse, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J","family":"Rooney","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Physiology, State University of New York Upstate Medical University , Syracuse, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A","family":"Middleton","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Physiology, State University of New York Upstate Medical University , Syracuse, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan H","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, State University of New York Upstate Medical University , Syracuse, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5696-0268","authenticated-orcid":false,"given":"Jeffrey R","family":"Currier","sequence":"additional","affiliation":[{"name":"Viral Diseases Branch, Walter Reed Army Institute of Research , Silver Spring, Maryland ,","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 New York Upstate Medical University , Syracuse, New York ,","place":["USA"]},{"name":"Institute for Global Health and Translational Sciences, State University of New York Upstate Medical University , Syracuse, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"2025013005310350600_ofae720-B1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of Dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"2025013005310350600_ofae720-B2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1093\/infdis\/140.4.527","article-title":"In vivo enhancement of Dengue virus infection in rhesus monkeys by passively transferred antibody","volume":"140","author":"Halstead","year":"1979","journal-title":"J Infect Dis"},{"key":"2025013005310350600_ofae720-B3","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.AID-0022-2014","article-title":"Dengue antibody-dependent enhancement: knowns and unknowns","volume":"2","author":"Halstead","year":"2014","journal-title":"Microbiol Spectr"},{"key":"2025013005310350600_ofae720-B4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1084\/jem.146.1.201","article-title":"Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody","volume":"146","author":"Halstead","year":"1977","journal-title":"J Exp Med"},{"key":"2025013005310350600_ofae720-B5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/infdis\/128.1.7","article-title":"Studies on the pathogenesis of Dengue infection in monkeys. I. Clinical laboratory responses to primary infection","volume":"128","author":"Halstead","year":"1973","journal-title":"J Infect Dis"},{"key":"2025013005310350600_ofae720-B6","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/infdis\/128.1.15","article-title":"Studies on the pathogenesis of Dengue infection in monkeys. II. Clinical laboratory responses to heterologous infection","volume":"128","author":"Halstead","year":"1973","journal-title":"J Infect Dis"},{"key":"2025013005310350600_ofae720-B7","doi-asserted-by":"crossref","first-page":"e721","DOI":"10.1371\/journal.pntd.0000721","article-title":"Structural optimization and de novo design of Dengue virus entry inhibitory peptides","volume":"4","author":"Costin","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"key":"2025013005310350600_ofae720-B8","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nature02165","article-title":"Structure of the Dengue virus envelope protein after membrane fusion","volume":"427","author":"Modis","year":"2004","journal-title":"Nature"},{"key":"2025013005310350600_ofae720-B9","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1146\/annurev.mi.44.100190.003245","article-title":"Flavivirus genome organization, expression, and replication","volume":"44","author":"Chambers","year":"1990","journal-title":"Annu Rev Microbiol"},{"key":"2025013005310350600_ofae720-B10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41426-018-0168-0","article-title":"Dengue virus and the host innate immune response","volume":"7","author":"Uno","year":"2018","journal-title":"Emerg Microbes Infect"},{"key":"2025013005310350600_ofae720-B11","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1172\/JCI21512","article-title":"Dengue: defining protective versus pathologic immunity","volume":"113","author":"Rothman","year":"2004","journal-title":"J Clin Invest"},{"key":"2025013005310350600_ofae720-B12","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":"2025013005310350600_ofae720-B13","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":"2025013005310350600_ofae720-B14","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":"2025013005310350600_ofae720-B15","doi-asserted-by":"crossref","first-page":"e1004386","DOI":"10.1371\/journal.ppat.1004386","article-title":"Dengue viruses are enhanced by distinct populations of serotype cross-reactive antibodies in human immune sera","volume":"10","author":"de Alwis","year":"2014","journal-title":"PLoS Pathog"},{"key":"2025013005310350600_ofae720-B16","doi-asserted-by":"crossref","first-page":"e1003157","DOI":"10.1371\/journal.ppat.1003157","article-title":"Therapeutic efficacy of antibodies lacking fcgamma receptor binding against lethal Dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies [corrected]","volume":"9","author":"Williams","year":"2013","journal-title":"PLoS Pathog"},{"key":"2025013005310350600_ofae720-B17","doi-asserted-by":"crossref","first-page":"777672","DOI":"10.3389\/fimmu.2021.777672","article-title":"Monomeric IgA antagonizes IgG-mediated enhancement of DENV infection","volume":"12","author":"Wegman","year":"2021","journal-title":"Front Immunol"},{"key":"2025013005310350600_ofae720-B18","doi-asserted-by":"crossref","first-page":"e1011616","DOI":"10.1371\/journal.ppat.1011616","article-title":"DENV-specific IgA contributes protective and non-pathologic function during antibody-dependent enhancement of DENV infection","volume":"19","author":"Wegman","year":"2023","journal-title":"PLoS Pathog"},{"key":"2025013005310350600_ofae720-B19","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/infdis\/jiad122","article-title":"Soluble NS1 antagonizes IgG- and IgA-mediated monocytic phagocytosis of DENV infected cells","volume":"228","author":"Waldran","year":"2023","journal-title":"J Infect Dis"},{"key":"2025013005310350600_ofae720-B20","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1002\/eji.1830270915","article-title":"Size-dependent effect of IgA on the IgA fc receptor (CD89)","volume":"27","author":"Reterink","year":"1997","journal-title":"Eur J Immunol"},{"key":"2025013005310350600_ofae720-B21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/microbiolspec.AID-0019-2014","article-title":"Functions of antibodies","volume":"2","author":"Forthal","year":"2014","journal-title":"Microbiol Spectr"},{"key":"2025013005310350600_ofae720-B22","doi-asserted-by":"crossref","first-page":"e151782","DOI":"10.1172\/jci.insight.151782","article-title":"Cross-reactive antibodies facilitate innate sensing of Dengue and Zika viruses","volume":"7","author":"Aisenberg","year":"2022","journal-title":"JCI Insight"},{"key":"2025013005310350600_ofae720-B23","doi-asserted-by":"crossref","first-page":"eabm3151","DOI":"10.1126\/scitranslmed.abm3151","article-title":"Antibody fc characteristics and effector functions correlate with protection from symptomatic Dengue virus type 3 infection","volume":"14","author":"Dias","year":"2022","journal-title":"Sci Transl Med"},{"key":"2025013005310350600_ofae720-B24","doi-asserted-by":"crossref","first-page":"9047","DOI":"10.1038\/s41598-020-65939-5","article-title":"Analysis of cell-associated DENV RNA by oligo(dT) primed 5\u2032 capture scRNAseq","volume":"10","author":"Sanborn","year":"2020","journal-title":"Sci Rep"},{"key":"2025013005310350600_ofae720-B25","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0168-1656(99)00037-1","article-title":"A recombinant fab neutralizes Dengue virus in vitro","volume":"69","author":"Thullier","year":"1999","journal-title":"J Biotechnol"},{"key":"2025013005310350600_ofae720-B26","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1099\/0022-1317-82-8-1885","article-title":"Mapping of a Dengue virus neutralizing epitope critical for the infectivity of all serotypes: insight into the neutralization mechanism","volume":"82","author":"Thullier","year":"2001","journal-title":"J Gen Virol"},{"key":"2025013005310350600_ofae720-B27","doi-asserted-by":"crossref","first-page":"7700","DOI":"10.1128\/JVI.00197-13","article-title":"Immature and mature Dengue serotype 1 virus structures provide insight into the maturation process","volume":"87","author":"Kostyuchenko","year":"2013","journal-title":"J Virol"},{"key":"2025013005310350600_ofae720-B28","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.virol.2015.08.011","article-title":"Comprehensive mapping of functional epitopes on Dengue virus glycoprotein E DIII for binding to broadly neutralizing antibodies 4E11 and 4E5A by phage display","volume":"485","author":"Frei","year":"2015","journal-title":"Virology"},{"key":"2025013005310350600_ofae720-B29","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat Methods"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofae720\/61052424\/ofae720.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/12\/1\/ofae720\/61052424\/ofae720.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/12\/1\/ofae720\/61052424\/ofae720.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:31:24Z","timestamp":1738197084000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofae720\/7921489"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,11]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,12,23]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofae720","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.07.21.604479","asserted-by":"object"}]},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,12,11]]},"article-number":"ofae720"}}