Characterization of Serotype-Specific Dengue Virus T-Cell Inhibition
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Le résumé fourni par la source
BACKGROUND: 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. METHODS: DENV serotype effects on human T-cell activation were assessed by measuring T-cell receptor (TCR)-mediated 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. RESULTS: 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. CONCLUSIONS: 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.
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DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Characterization of Serotype-Specific Dengue Virus T-Cell Inhibition
- Date Crossref
- 08/05/2025
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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University of Iowa Department of Microbiology and Immunology pays non établi dans la noticeUniversité ou école supérieure
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Department of Microbiology and Immunology — University of Iowa, Iowa City VA Health Care System et Iowa City VA Medical Center, avec 7 autres affiliations.
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