{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T13:06:09Z","timestamp":1763816769722,"version":"3.45.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","funder":[{"name":"Veterans Affairs Merit Review","award":["BX000207"],"award-info":[{"award-number":["BX000207"]}]},{"DOI":"10.13039\/100006380","name":"Veterans Affairs VA SeqCURE program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006380","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5T32AI343","P30 CA086862"],"award-info":[{"award-number":["5T32AI343","P30 CA086862"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008893","name":"Human Immunology Core, University of Iowa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008893","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI170205","R01 AI107301","U19A171401"],"award-info":[{"award-number":["R01AI170205","R01 AI107301","U19A171401"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"name":"predoctoral fellowship by the China Research Council"},{"DOI":"10.13039\/100015515","name":"University of Iowa Carver College of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015515","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dengue virus serotype 2 and 3 (DENV-2 and -3) infections are associated with more severe disease outcomes than DENV-1 and 4, though a biological explanation for this has not been identified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>DENV serotype effects on human T-cell activation were assessed by measuring T-cell receptor (TCR)\u2013mediated interleukin 2 release following TCR stimulation. DENV envelope (env) proteins were expressed in Jurkat CD4+ T-cell lines, and regions inhibiting TCR inhibition were mapped by mutagenesis. TCR signaling pathway inhibition was characterized by total internal reflection fluorescence microscopy and immunoblot. Reverse genetics validated env mapping results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>T-cell incubation with DENV-1 and -4 inhibited TCR signaling, whereas DENV-2 and -3 did not. Inhibition did not require viral replication. DENV env protein expression inhibited TCR by interfering with activation of proximal TCR signaling events. Amino acids (aa's) 49 to 62 of DENV 1 env were sufficient to inhibit TCR signaling, with env aa's 55 and 66 being critical. Reverse genetics confirmed that substitution of DENV-2 and -3 aa's 55 and 66 into DENV-1 and -4 reversed TCR inhibition and that DENV-1 aa's 55 and 66 introduced into DENV-2 and -3 enabled TCR inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DENV-2 and -3 are associated with more severe clinical disease than DENV-1 and -4; however, no biological explanation for this difference has been previously identified. We found that DENV-1 and -4 viral particles and env proteins blunt T-cell responses by interfering with proximal TCR signaling, while DENV-2 and -3 do not, potentially explaining DENV pathogenic outcomes in primary and secondary infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf241","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T03:01:22Z","timestamp":1746673282000},"page":"1228-1238","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of Serotype-Specific Dengue Virus T-Cell Inhibition"],"prefix":"10.1093","volume":"232","author":[{"given":"Jinhua","family":"Xiang","sequence":"first","affiliation":[{"name":"Medical and Research Services, Iowa City VA HealthCare"},{"name":"Department of Internal Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James H","family":"McLinden","sequence":"additional","affiliation":[{"name":"Medical and Research Services, Iowa City VA 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