{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:00:40Z","timestamp":1791655240398,"version":"4.3.4"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001475","name":"Nanyang Technological University","doi-asserted-by":"publisher","award":["Research Scholarship Block"],"award-info":[{"award-number":["Research Scholarship Block"]}],"id":[{"id":"10.13039\/501100001475","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011738","name":"Lee Kong Chian School of Medicine, Nanyang Technological University","doi-asserted-by":"publisher","award":["Start up Grant"],"award-info":[{"award-number":["Start up Grant"]}],"id":[{"id":"10.13039\/501100011738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education Fundamental Research Grant Scheme of Malaysia","award":["FRGS\/1\/2020\/SKK0\/TAYLOR\/02\/1"],"award-info":[{"award-number":["FRGS\/1\/2020\/SKK0\/TAYLOR\/02\/1"]}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"crossref","award":["NMRC\/Fellowship\/0056\/2018"],"award-info":[{"award-number":["NMRC\/Fellowship\/0056\/2018"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011738","name":"Lee Kong Chian School of Medicine, Nanyang Technological University","doi-asserted-by":"publisher","award":["Start up Grant"],"award-info":[{"award-number":["Start up Grant"]}],"id":[{"id":"10.13039\/501100011738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001475","name":"Nanyang Technological University","doi-asserted-by":"publisher","award":["Research Scholarship Block"],"award-info":[{"award-number":["Research Scholarship Block"]}],"id":[{"id":"10.13039\/501100001475","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011738","name":"Lee Kong Chian School of Medicine, Nanyang Technological University","doi-asserted-by":"publisher","award":["Start up Grant"],"award-info":[{"award-number":["Start up Grant"]}],"id":[{"id":"10.13039\/501100011738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education Fundamental Research Grant Scheme of Malaysia","award":["FRGS\/1\/2020\/SKK0\/TAYLOR\/02\/1"],"award-info":[{"award-number":["FRGS\/1\/2020\/SKK0\/TAYLOR\/02\/1"]}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"crossref","award":["NMRC\/Fellowship\/0056\/2018"],"award-info":[{"award-number":["NMRC\/Fellowship\/0056\/2018"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011738","name":"Lee Kong Chian School of Medicine, Nanyang Technological University","doi-asserted-by":"publisher","award":["Start up Grant"],"award-info":[{"award-number":["Start up Grant"]}],"id":[{"id":"10.13039\/501100011738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001475","name":"Nanyang Technological University","doi-asserted-by":"publisher","award":["Research Scholarship Block"],"award-info":[{"award-number":["Research Scholarship Block"]}],"id":[{"id":"10.13039\/501100001475","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011738","name":"Lee Kong Chian School of Medicine, Nanyang Technological University","doi-asserted-by":"publisher","award":["Start up Grant"],"award-info":[{"award-number":["Start up Grant"]}],"id":[{"id":"10.13039\/501100011738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education Fundamental Research Grant Scheme of Malaysia","award":["FRGS\/1\/2020\/SKK0\/TAYLOR\/02\/1"],"award-info":[{"award-number":["FRGS\/1\/2020\/SKK0\/TAYLOR\/02\/1"]}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"crossref","award":["NMRC\/Fellowship\/0056\/2018"],"award-info":[{"award-number":["NMRC\/Fellowship\/0056\/2018"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011738","name":"Lee Kong Chian School of Medicine, Nanyang Technological University","doi-asserted-by":"publisher","award":["Start up Grant"],"award-info":[{"award-number":["Start up Grant"]}],"id":[{"id":"10.13039\/501100011738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1010065","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T18:23:42Z","timestamp":1639074222000},"page":"e1010065","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":41,"title":["Insights into potential causes of vascular hyperpermeability in dengue"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4520-2701","authenticated-orcid":true,"given":"Andrew","family":"Teo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6974-1750","authenticated-orcid":true,"given":"Caroline Lin Lin","family":"Chua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8797-9527","authenticated-orcid":true,"given":"Po Ying","family":"Chia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsin Wen","family":"Yeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"ppat.1010065.ref001","article-title":"Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control","author":"World Health Organization","year":"2009"},{"issue":"42","key":"ppat.1010065.ref002","doi-asserted-by":"crossref","first-page":"7221","DOI":"10.1016\/j.vaccine.2011.07.022","article-title":"The pathogenesis of dengue","volume":"29","author":"J Whitehorn","year":"2011","journal-title":"Vaccine"},{"key":"ppat.1010065.ref003","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3389\/fcimb.2020.572681","article-title":"Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine","volume":"10","author":"R Shukla","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"issue":"3","key":"ppat.1010065.ref004","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/imm.12748","article-title":"Pathogenesis of vascular leak in dengue virus infection","volume":"151","author":"GN Malavige","year":"2017","journal-title":"Immunology"},{"key":"ppat.1010065.ref005","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.ebiom.2019.09.014","article-title":"High levels of serum hyaluronan is an early predictor of dengue warning signs and perturbs vascular integrity.","volume":"48","author":"CY Lin","year":"2019","journal-title":"EBioMedicine"},{"key":"ppat.1010065.ref006","doi-asserted-by":"crossref","first-page":"46191","DOI":"10.1038\/srep46191","article-title":"Increased Serum Hyaluronic Acid and Heparan Sulfate in Dengue Fever: Association with Plasma Leakage and Disease Severity.","volume":"7","author":"TH Tang","year":"2017","journal-title":"Sci Rep"},{"issue":"11","key":"ppat.1010065.ref007","doi-asserted-by":"crossref","first-page":"e1006673","DOI":"10.1371\/journal.ppat.1006673","article-title":"Dengue virus NS1 cytokine-independent vascular leak is dependent on endothelial glycocalyx components.","volume":"13","author":"DR Glasner","year":"2017","journal-title":"PLoS Pathog"},{"issue":"7","key":"ppat.1010065.ref008","doi-asserted-by":"crossref","first-page":"e1005738","DOI":"10.1371\/journal.ppat.1005738","article-title":"Dengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability.","volume":"12","author":"H Puerta-Guardo","year":"2016","journal-title":"PLoS Pathog"},{"key":"ppat.1010065.ref009","doi-asserted-by":"crossref","first-page":"545813","DOI":"10.3389\/fmed.2020.545813","article-title":"Visual and Biochemical Evidence of Glycocalyx Disruption in Human Dengue Infection, and Association With Plasma Leakage Severity.","volume":"7","author":"PK Lam","year":"2020","journal-title":"Front Med"},{"issue":"6","key":"ppat.1010065.ref010","first-page":"992","article-title":"Association of Endothelial Glycocalyx and Tight and Adherens Junctions With Severity of Plasma Leakage in Dengue Infection","volume":"215","author":"S Suwarto","year":"2017","journal-title":"J Infect Dis"},{"key":"ppat.1010065.ref011","first-page":"1","article-title":"The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases.","volume":"2020","author":"S Weinbaum","journal-title":"Cardiovasc Eng Technol"},{"issue":"19","key":"ppat.1010065.ref012","doi-asserted-by":"crossref","first-page":"8003","DOI":"10.1073\/pnas.1017338108","article-title":"Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein","volume":"108","author":"I Gutsche","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"ppat.1010065.ref013","doi-asserted-by":"crossref","first-page":"e1008603","DOI":"10.1371\/journal.ppat.1008603","article-title":"DENV NS1 and MMP-9 cooperate to induce vascular leakage by altering endothelial cell adhesion and tight junction","volume":"17","author":"P Pan","journal-title":"PLoS Pathog. 2021"},{"issue":"8","key":"ppat.1010065.ref014","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1086\/343813","article-title":"High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever","volume":"186","author":"DH Libraty","year":"2002","journal-title":"J Infect Dis"},{"issue":"8","key":"ppat.1010065.ref015","doi-asserted-by":"crossref","first-page":"e0237141","DOI":"10.1371\/journal.pone.0237141","article-title":"Correlation of host inflammatory cytokines and immune-related metabolites, but not viral NS1 protein, with disease severity of dengue virus infection.","volume":"15","author":"HJ Soe","year":"2020","journal-title":"PLoS ONE"},{"issue":"11","key":"ppat.1010065.ref016","doi-asserted-by":"crossref","first-page":"e113634","DOI":"10.1371\/journal.pone.0113634","article-title":"Assessing positivity and circulating levels of NS1 in samples from a 2012 dengue outbreak in Rio de Janeiro, Brazil.","volume":"9","author":"D Allonso","year":"2014","journal-title":"PLoS ONE"},{"issue":"3","key":"ppat.1010065.ref017","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1128\/JCM.38.3.1053-1057.2000","article-title":"An antigen capture enzyme-linked immunosorbent assay reveals high levels of the dengue virus protein NS1 in the sera of infected patients","volume":"38","author":"PR Young","year":"2000","journal-title":"J Clin Microbiol"},{"issue":"1","key":"ppat.1010065.ref018","first-page":"227","article-title":"The Good, the Bad, and the Shocking: The Multiple Roles of Dengue Virus Nonstructural Protein 1 in Protection and Pathogenesis.","volume":"5","author":"DR Glasner","year":"2018","journal-title":"Annu Rev"},{"issue":"12","key":"ppat.1010065.ref019","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1099\/jgv.0.001163","article-title":"Dengue virus or NS1 protein induces trans-endothelial cell permeability associated with VE-Cadherin and RhoA phosphorylation in HMEC-1 cells preventable by Angiopoietin-1","volume":"99","author":"S Singh","year":"2018","journal-title":"J Gen Virol"},{"issue":"304","key":"ppat.1010065.ref020","doi-asserted-by":"crossref","first-page":"304ra142","DOI":"10.1126\/scitranslmed.aaa3863","article-title":"Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity.","volume":"7","author":"N Modhiran","year":"2015","journal-title":"Sci Transl Med"},{"issue":"4","key":"ppat.1010065.ref021","doi-asserted-by":"crossref","first-page":"e1007033","DOI":"10.1371\/journal.ppat.1007033","article-title":"Macrophage migration inhibitory factor is critical for dengue NS1-induced endothelial glycocalyx degradation and hyperpermeability.","volume":"14","author":"HR Chen","year":"2018","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1010065.ref022","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1093\/infdis\/jiw494","article-title":"Severity of Plasma Leakage Is Associated With High Levels of Interferon \u03b3-Inducible Protein 10, Hepatocyte Growth Factor, Matrix Metalloproteinase 2 (MMP-2), and MMP-9 During Dengue Virus Infection.","volume":"215","author":"Z Her","year":"2017","journal-title":"J Infect Dis"},{"issue":"322","key":"ppat.1010065.ref023","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/1743-422X-10-322","article-title":"Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection.","volume":"10","author":"WM Loke","year":"2013","journal-title":"Virol J"},{"issue":"24","key":"ppat.1010065.ref024","doi-asserted-by":"crossref","first-page":"12982","DOI":"10.1128\/JVI.01224-10","article-title":"The early whole-blood transcriptional signature of dengue virus and features associated with progression to dengue shock syndrome in Vietnamese children and young adults","volume":"84","author":"LT Hoang","year":"2010","journal-title":"J Virol"},{"issue":"7","key":"ppat.1010065.ref025","doi-asserted-by":"crossref","first-page":"e11671","DOI":"10.1371\/journal.pone.0011671","article-title":"Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue","volume":"5","author":"S Devignot","year":"2010","journal-title":"PLoS ONE"},{"issue":"3007","key":"ppat.1010065.ref026","first-page":"3007","article-title":"Neutrophil Activation and Early Features of NET Formation Are Associated With Dengue Virus Infection in Human.","volume":"9","author":"A Opasawatchai","year":"2018","journal-title":"Front Immunol"},{"issue":"2","key":"ppat.1010065.ref027","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/s12291-017-0658-1","article-title":"Plasma Neutrophil Elastase, \u03b1(1)-Antitrypsin, \u03b1(2)-Macroglobulin and Neutrophil Elastase-\u03b1(1)-Antitrypsin Complex Levels in patients with Dengue Fever.","volume":"33","author":"M Kunder","year":"2018","journal-title":"Indian J Clin Biochem"},{"issue":"2","key":"ppat.1010065.ref028","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1128\/IAI.68.2.702-707.2000","article-title":"Inflammatory mediators in dengue virus infection in children: interleukin-8 and its relationship to neutrophil degranulation","volume":"68","author":"M Juffrie","year":"2000","journal-title":"Infect Immun"},{"key":"ppat.1010065.ref029","doi-asserted-by":"crossref","first-page":"629167","DOI":"10.3389\/fimmu.2021.629167","article-title":"Neutrophil Extracellular Traps in Dengue Are Mainly Generated NOX-Independently.","volume":"12","author":"FM Garishah","year":"2021","journal-title":"Front Immunol."},{"issue":"1","key":"ppat.1010065.ref030","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1038\/s41467-019-10360-4","article-title":"Extracellular vesicles from CLEC2-activated platelets enhance dengue virus-induced lethality via CLEC5A\/TLR2.","volume":"10","author":"PS Sung","year":"2019","journal-title":"Nat Commun"},{"issue":"6","key":"ppat.1010065.ref031","doi-asserted-by":"crossref","first-page":"984","DOI":"10.4269\/ajtmh.14-0004","article-title":"Severe neutropenia in dengue patients: prevalence and significance","volume":"90","author":"TL Thein","year":"2014","journal-title":"Am J Trop Med Hyg"},{"issue":"10","key":"ppat.1010065.ref032","doi-asserted-by":"crossref","first-page":"4180","DOI":"10.1172\/JCI128426","article-title":"Dengue virus-elicited tryptase induces endothelial permeability and shock","volume":"129","author":"AP Rathore","year":"2019","journal-title":"J Clin Invest"},{"issue":"2","key":"ppat.1010065.ref033","doi-asserted-by":"crossref","first-page":"e00481","DOI":"10.7554\/eLife.00481","article-title":"Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage.","volume":"2","author":"AL St John","year":"2013","journal-title":"Elife"},{"issue":"4","key":"ppat.1010065.ref034","first-page":"05291","article-title":"Dengue vascular leakage is augmented by mast cell degranulation mediated by immunoglobulin Fc\u03b3 receptors","volume":"4","author":"A Syenina","year":"2015","journal-title":"Elife"},{"issue":"2","key":"ppat.1010065.ref035","doi-asserted-by":"crossref","first-page":"e1505","DOI":"10.1371\/journal.pntd.0001505","article-title":"Association of mast cell-derived VEGF and proteases in Dengue shock syndrome","volume":"6","author":"T Furuta","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"issue":"20","key":"ppat.1010065.ref036","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.1182\/blood-2013-05-504449","article-title":"Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation","volume":"122","author":"ED Hottz","year":"2013","journal-title":"Blood"},{"issue":"4","key":"ppat.1010065.ref037","doi-asserted-by":"crossref","first-page":"e1007625","DOI":"10.1371\/journal.ppat.1007625","article-title":"Dengue virus nonstructural protein 1 activates platelets via Toll-like receptor 4, leading to thrombocytopenia and hemorrhage.","volume":"15","author":"CH Chao","year":"2019","journal-title":"PLoS Pathog"},{"issue":"5","key":"ppat.1010065.ref038","doi-asserted-by":"crossref","first-page":"e1006385","DOI":"10.1371\/journal.ppat.1006385","article-title":"Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue.","volume":"13","author":"MRO Trugilho","year":"2017","journal-title":"PLoS Pathog"},{"issue":"4","key":"ppat.1010065.ref039","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.4049\/jimmunol.1400091","article-title":"Platelet activation and apoptosis modulate monocyte inflammatory responses in dengue","volume":"193","author":"ED Hottz","year":"2014","journal-title":"J Immunol"},{"issue":"7446","key":"ppat.1010065.ref040","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"S Bhatt","year":"2013","journal-title":"Nature"},{"issue":"1","key":"ppat.1010065.ref041","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/imm.12492","article-title":"Mast cell-macrophage dynamics in modulation of dengue virus infection in skin","volume":"146","author":"YT Chu","year":"2015","journal-title":"Immunology"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T18:24:14Z","timestamp":1639074254000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010065"}},"subtitle":[],"editor":[{"given":"Wendy","family":"Maury","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,12,9]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010065","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,9]]}}}