{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:34:24Z","timestamp":1790904864394,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2009,8,1]],"date-time":"2009-08-01T00:00:00Z","timestamp":1249084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The mechanisms underlying dengue hemorrhagic disease are incompletely understood. We previously showed that anti-dengue virus (DV) nonstructural protein 1 (NS1) Abs cross-react with human platelets and inhibit platelet aggregation. Based on sequence homology alignment, the cross-reactive epitopes reside in the C-terminal region of DV NS1. In this study, we compared the effects of Abs against full-length DV NS1 and NS1 lacking the C-terminal aa 271 to 352 (designated \u0394C NS1). Anti-\u0394C NS1 Abs exhibited lower platelet binding activity than that of anti-full-length NS1. Anti-full-length NS1 but not anti-\u0394C NS1 Abs inhibited platelet aggregation, which was shown to involve integrin \u03b1IIb\u03b23 inactivation. We found that the bleeding time in full-length NS1-hyperimmunized mice was longer than that in the normal control mice. By contrast, \u0394C NS1-hyperimmunized mice showed a bleeding time similar to that of normal control mice. Passively administered anti-DV NS1, but not anti-\u0394C NS1, Ab level decreased markedly in serum and this decrease was correlated with Ab binding to platelets. A transient platelet loss in the circulation was observed after anti-DV NS1, but not anti-\u0394C NS1, Ab administration. In summary, platelet dysfunction and bleeding tendency are induced by anti-full-length DV NS1 but not by anti-\u0394C NS1 Abs. These findings may be important not only for understanding dengue hemorrhagic disease pathogenesis but also for dengue vaccine development.<\/jats:p>","DOI":"10.4049\/jimmunol.0800672","type":"journal-article","created":{"date-parts":[[2009,7,11]],"date-time":"2009-07-11T01:40:49Z","timestamp":1247276449000},"page":"1797-1803","source":"Crossref","is-referenced-by-count":67,"title":["Deletion of the C-Terminal Region of Dengue Virus Nonstructural Protein 1 (NS1) Abolishes Anti-NS1-Mediated Platelet Dysfunction and Bleeding Tendency"],"prefix":"10.1093","volume":"183","author":[{"given":"Mei-Chun","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiou-Feng","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan-Yao","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Chao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Sheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trai-Ming","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University , Halifax, Nova Scotia,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee-Shin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"},{"name":"Center for Gene Regulation and Signal Transduction Research, National Cheng Kung University Medical College , Tainan,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,8,1]]},"reference":[{"key":"2025032709085394500_R1","first-page":"376","article-title":"The dengue viruses.","volume-title":"Clin. Microbiol. Rev.","year":"1990"},{"key":"2025032709085394500_R2","first-page":"480","article-title":"Dengue and dengue hemorrhagic fever.","volume-title":"Clin. Microbiol. Rev.","year":"1998"},{"key":"2025032709085394500_R3","first-page":"429","article-title":"Immunopathological mechanisms in dengue and dengue hemorrhagic fever.","volume-title":"Curr. Opin. Infect. Dis.","year":"2006"},{"key":"2025032709085394500_R4","first-page":"11418","article-title":"Recent advances in deciphering viral and host determinants of dengue virus replication and pathogenesis.","volume-title":"J. Virol.","year":"2006"},{"key":"2025032709085394500_R5","first-page":"1644","article-title":"Dengue.","volume-title":"Lancet","year":"2007"},{"key":"2025032709085394500_R6","first-page":"377","article-title":"Immunopathogenesis of dengue virus infection.","volume-title":"J. Biomed. Sci.","year":"2001"},{"key":"2025032709085394500_R7","first-page":"263","article-title":"Role of T cells, cytokines and antibody in dengue fever and dengue haemorrhagic fever.","volume-title":"Rev. Med. Virol.","year":"2006"},{"key":"2025032709085394500_R8","first-page":"43","article-title":"Of cascades and perfect storms: the immunopathogenesis of dengue haemorrhagic fever-dengue shock syndrome (DHF\/DSS).","volume-title":"Immunol. Cell Biol.","year":"2007"},{"key":"2025032709085394500_R9","first-page":"506","article-title":"Human T cell responses to dengue virus antigens: proliferative responses and interferon \u03b3 production.","volume-title":"J. Clin. Invest.","year":"1989"},{"key":"2025032709085394500_R10","first-page":"7146","article-title":"Release of vasoactive cytokines by antibody-enhanced dengue virus infection of a human mast cell\/basophil line.","volume-title":"J. Virol.","year":"2000"},{"key":"2025032709085394500_R11","first-page":"6338","article-title":"Dengue virus infection of human endothelial cells leads to chemokine production, complement activation, and apoptosis.","volume-title":"J. Immunol.","year":"1998"},{"key":"2025032709085394500_R12","first-page":"1529","article-title":"Heterogeneity of infection enhancement of dengue 2 strains by monoclonal antibodies.","volume-title":"J. Immunol.","year":"1984"},{"key":"2025032709085394500_R13","first-page":"3183","article-title":"Human IgG Fc receptor II mediates antibody-dependent enhancement of dengue virus infection.","volume-title":"J. Immunol.","year":"1990"},{"key":"2025032709085394500_R14","first-page":"3139","article-title":"Antibody-dependent enhancement of dengue virus infection mediated by bispecific antibodies against cell surface molecules other than Fc\u03b3 receptors.","volume-title":"J. Immunol.","year":"1991"},{"key":"2025032709085394500_R15","first-page":"500","article-title":"Antibody-dependent enhancement of infection and the pathogenesis of viral disease.","volume-title":"Clin. Infect. Dis.","year":"1994"},{"key":"2025032709085394500_R16","first-page":"4226","article-title":"Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes.","volume-title":"J. Virol.","year":"1997"},{"key":"2025032709085394500_R17","first-page":"2825","article-title":"The dual-specific binding of dengue virus and target cells for the antibody-dependent enhancement of dengue virus infection.","volume-title":"J. Immunol.","year":"2006"},{"key":"2025032709085394500_R18","first-page":"1242","article-title":"A dominant role for Fc\u03b3RII in antibody-enhanced dengue virus infection of human mast cells and associated CCL5 release.","volume-title":"J. Leukocyte Biol.","year":"2006"},{"key":"2025032709085394500_R19","first-page":"897","article-title":"The dengue virus nonstructural-1 protein (NS1) generates antibodies to common epitopes on human blood clotting, integrin\/adhesin proteins and binds to human endothelial cells: potential implications in haemorrhagic fever pathogenesis.","volume-title":"Arch. Virol.","year":"1997"},{"key":"2025032709085394500_R20","first-page":"143","article-title":"Generation of IgM anti-platelet autoantibody in dengue patients.","volume-title":"J. Med. Virol.","year":"2001"},{"key":"2025032709085394500_R21","first-page":"82","article-title":"Antibodies from dengue patient sera cross-react with endothelial cells and induce damage.","volume-title":"J. Med. Virol.","year":"2003"},{"key":"2025032709085394500_R22","first-page":"657","article-title":"Endothelial cell apoptosis induced by antibodies against dengue virus nonstructural protein 1 via production of nitric oxide.","volume-title":"J. Immunol.","year":"2002"},{"key":"2025032709085394500_R23","first-page":"213","article-title":"Antibody-mediated endothelial cell damage via nitric oxide.","volume-title":"Curr. Pharm. Design","year":"2004"},{"key":"2025032709085394500_R24","first-page":"395","article-title":"Expression of cytokine, chemokine, and adhesion molecules during endothelial cell activation induced by antibodies against dengue virus nonstructural protein 1.","volume-title":"J. Immunol.","year":"2005"},{"key":"2025032709085394500_R25","first-page":"127","article-title":"Autoimmune pathogenesis in dengue virus infection.","volume-title":"Viral Immunol.","year":"2006"},{"key":"2025032709085394500_R26","first-page":"513","article-title":"Platelet autoantibodies are common in hepatitis C infection, irrespective of the presence of thrombocytopenia.","volume-title":"Eur. J. Haematol.","year":"2006"},{"key":"2025032709085394500_R27","first-page":"621","article-title":"Thrombocytopenic purpura in cytomegalovirus mononucleosis.","volume-title":"Lancet","year":"1973"},{"key":"2025032709085394500_R28","first-page":"162","article-title":"Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombocytopenic purpura.","volume-title":"Blood","year":"1992"},{"key":"2025032709085394500_R29","first-page":"1561","article-title":"Platelet activation: assessment and quantification.","volume-title":"Eur. Heart J.","year":"2001"},{"key":"2025032709085394500_R30","first-page":"85","article-title":"C-terminal region of dengue virus nonstructural protein 1 is involved in endothelial cell cross-reactivity via molecular mimicry.","volume-title":"Am. J. Infect. Dis.","year":"2008"},{"key":"2025032709085394500_R31","first-page":"63","article-title":"Proteomic analysis of endothelial cell autoantigens recognized by anti-dengue virus nonstructural protein 1 antibodies.","volume-title":"Exp. Biol. Med.","year":"2009"},{"key":"2025032709085394500_R32","first-page":"944","article-title":"Deficiency of Src homology 2 domain-containing inositol 5-phosphatase 1 affects platelet responses and thrombus growth.","volume-title":"J. Clin. Invest.","year":"2007"},{"key":"2025032709085394500_R33","first-page":"862","article-title":"Correction of a murine model of von Willebrand disease by gene transfer.","volume-title":"Blood","year":"2006"},{"key":"2025032709085394500_R34","first-page":"69","article-title":"Patient and mouse antibodies against dengue virus nonstructural protein 1 cross-react with platelets and cause their dysfunction or depletion.","volume-title":"Am. J. Infect. Dis.","year":"2008"},{"key":"2025032709085394500_R35","first-page":"604","article-title":"Platelet \u03b1-granule proteins: studies on release and subcellular localization.","volume-title":"Blood","year":"1979"},{"key":"2025032709085394500_R36","first-page":"3334","article-title":"Molecular mechanisms of platelet exocytosis: insights into the \u201csecrete\u201d life of thrombocytes.","volume-title":"Blood","year":"2000"},{"key":"2025032709085394500_R37","first-page":"261","article-title":"The platelet release reaction: granules\u2019 constituents, secretion and functions.","volume-title":"Platelets","year":"2001"},{"key":"2025032709085394500_R38","first-page":"293","article-title":"Development of platelet secretory granules.","volume-title":"Semin. Cell Dev. Biol.","year":"2002"},{"key":"2025032709085394500_R39","first-page":"116","article-title":"Increased platelet activation and abnormal membrane glycoprotein content and redistribution in myeloproliferative disorders.","volume-title":"Br. J. Haematol.","year":"2000"},{"key":"2025032709085394500_R40","first-page":"2313","article-title":"Multivesicular bodies are an intermediate stage in the formation of platelet \u03b1-granules.","volume-title":"Blood","year":"1998"},{"key":"2025032709085394500_R41","first-page":"3782","article-title":"Regulation of platelet granule exocytosis by S-nitrosylation.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2005"},{"key":"2025032709085394500_R42","first-page":"199","article-title":"Plasma levels of \u03b2-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo.","volume-title":"Blood","year":"1981"},{"key":"2025032709085394500_R43","first-page":"96","article-title":"Integrin \u03b1IIb\u03b23 and platelet function.","volume-title":"Thromb. Haemost.","year":"1997"},{"key":"2025032709085394500_R44","first-page":"2645","article-title":"Integrin signaling: the platelet paradigm.","volume-title":"Blood","year":"1998"},{"key":"2025032709085394500_R45","first-page":"7345","article-title":"Effect of platelet activation on the conformation of the plasma membrane glycoprotein IIb-IIIa complex.","volume-title":"J. Biol. Chem.","year":"1991"},{"key":"2025032709085394500_R46","first-page":"1497","article-title":"Dengue virus inhibits human hematopoietic progenitor growth in vitro.","volume-title":"J. Infect. Dis.","year":"1997"},{"key":"2025032709085394500_R47","first-page":"254","article-title":"Antibody-enhanced binding of dengue-2 virus to human platelets.","volume-title":"Virology","year":"1995"},{"key":"2025032709085394500_R48","first-page":"2291","article-title":"Antiplatelet autoantibodies elicited by dengue virus non-structural protein 1 cause thrombocytopenia and mortality in mice.","volume-title":"J. Thromb. Haemost.","year":"2007"},{"key":"2025032709085394500_R49","first-page":"275","article-title":"Platelet\u2013vessel wall interactions in the microcirculation.","volume-title":"Microcirculation","year":"2005"},{"key":"2025032709085394500_R50","first-page":"1242","article-title":"Stimulation of thrombopoiesis in mice by human recombinant interleukin 6.","volume-title":"J. Clin. Invest.","year":"1990"},{"key":"2025032709085394500_R51","first-page":"2720","article-title":"Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis.","volume-title":"Blood","year":"2001"},{"key":"2025032709085394500_R52","first-page":"51","article-title":"Autoimmunity in dengue virus infection.","volume-title":"Dengue Bull.","year":"2004"},{"key":"2025032709085394500_R53","first-page":"1079","article-title":"Liver injury caused by antibodies against dengue virus nonstructural protein 1 in a murine model.","volume-title":"Lab. Invest.","year":"2008"},{"key":"2025032709085394500_R54","first-page":"2168","article-title":"Localization of protein disulfide isomerase to the external surface of the platelet plasma membrane.","volume-title":"Blood","year":"1995"},{"key":"2025032709085394500_R55","first-page":"448","article-title":"Protein disulphide isomerase mediates platelet aggregation and secretion.","volume-title":"Br. J. Haematol.","year":"1999"},{"key":"2025032709085394500_R56","first-page":"35","article-title":"Protein disulfide isomerase.","volume-title":"Biochim. Biophys. Acta","year":"2004"},{"key":"2025032709085394500_R57","first-page":"89","article-title":"Protein disulfide isomerase mediates integrin-dependent adhesion.","volume-title":"FEBS Lett.","year":"2000"},{"key":"2025032709085394500_R58","first-page":"2549","article-title":"Purified dengue 2 virus envelope glycoprotein aggregates produced by baculovirus are immunogenic in mice.","volume-title":"Vaccine","year":"2000"},{"key":"2025032709085394500_R59","first-page":"335","article-title":"Tetravalent neutralizing antibody response against four dengue serotypes by a single chimeric dengue envelope antigen.","volume-title":"Vaccine","year":"2006"},{"key":"2025032709085394500_R60","first-page":"89","article-title":"Immunoreactivity and protective effects in mice of a recombinant dengue 2 Tonga virus NS1 protein produced in a baculovirus expression system.","volume-title":"J. Gen. Virol.","year":"1993"},{"key":"2025032709085394500_R61","first-page":"4562","article-title":"DNA vaccine against the non-structural 1 protein (NS1) of dengue 2 virus.","volume-title":"Vaccine","year":"2006"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/3\/1797\/62697371\/9423.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/3\/1797\/62697371\/9423.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T10:58:14Z","timestamp":1743332294000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/183\/3\/1797\/8053791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,8,1]]},"references-count":61,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,8,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0800672","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,8]]},"published":{"date-parts":[[2009,8,1]]}}}