Stereochemical features of the envelope protein Domain III of dengue virus reveals putative antigenic site in the five-fold symmetry axis

ABSTRACT The surface of the mature dengue virus (DENV) particle is covered with 180 envelope (E) proteins arranged as homodimers that lie relatively flat on the virion surface. Each monomer consists of three domains (ED1, ED2, and ED3), of which ED3 contains the critical neutralization determinant(s). In this study, a large panel of DENV-2 recombinant ED3 mutant proteins was used to physically and biologically map the epitopes of five DENV complex-specific monoclonal antibodies (MAbs). All five MAbs recognized a single antigenic site that includes residues K310, I312, P332, L389, and W391. The DENV complex antigenic site was located on an upper lateral surface of ED3 that was distinct but overlapped with a previously described DENV-2 type-specific antigenic site on ED3. The DENV complex-specific MAbs required significantly higher occupancy levels of available ED3 binding sites on the virion, compared to DENV-2 type-specific MAbs, in order to neutralize virus infectivity. Additionally, there was a great deal of variability in the neutralization efficacy of the DENV complex-specific MAbs with representative strains of the four DENVs. Overall, the differences in physical binding and potency of neutralization observed between DENV complex- and type-specific MAbs in this study demonstrate the critical role of the DENV type-specific antibodies in the neutralization of virus infectivity.

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Anti-dengue virus envelope protein domain III IgG ELISA among infants with primary dengue virus infections

Acta Tropica ◽

10.1016/j.actatropica.2014.11.009 ◽

2015 ◽

Vol 142 ◽

pp. 103-107 ◽

Cited By ~ 4

Author(s):

Daniel H. Libraty ◽

Lei Zhang ◽

AnaMae Obcena ◽

Job D. Brion ◽

Rosario Z. Capeding

Keyword(s):

Dengue Virus ◽

Envelope Protein ◽

Protein Domain ◽

Virus Infections ◽

Virus Envelope ◽

Virus Envelope Protein ◽

Domain Iii

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Bacterially expressed and refolded envelope protein (domain III) of dengue virus type-4 binds heparan sulfate

Journal of Chromatography B ◽

10.1016/j.jchromb.2006.08.051 ◽

2007 ◽

Vol 846 (1-2) ◽

pp. 184-194 ◽

Cited By ~ 20

Author(s):

Priyabrata Pattnaik ◽

J. Pradeep Babu ◽

Shailendra Kumar Verma ◽

Vijay Tak ◽

P.V. Lakshmana Rao

Keyword(s):

Dengue Virus ◽

Heparan Sulfate ◽

Virus Type ◽

Envelope Protein ◽

Protein Domain ◽

Domain Iii

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Paradoxical Role of Dengue Virus Envelope Protein Domain III Antibodies in Dengue Virus Infection

Critical Reviews in Eukaryotic Gene Expression ◽

10.1615/critreveukaryotgeneexpr.2020028598 ◽

2020 ◽

Vol 30 (3) ◽

pp. 199-206

Author(s):

Sheeza Ali ◽

Samia Afzal ◽

Muhammad Zubair Yousaf ◽

Muhammad Shahid ◽

Iram Amin ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Envelope Protein ◽

Protein Domain ◽

Virus Envelope ◽

Dengue Virus Infection ◽

Virus Envelope Protein ◽

Domain Iii

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Production of dengue virus envelope protein domain III-based antigens in tobacco chloroplasts using inducible and constitutive expression systems

Plant Molecular Biology ◽

10.1007/s11103-016-0484-5 ◽

2016 ◽

Vol 91 (4-5) ◽

pp. 497-512 ◽

Cited By ~ 15

Author(s):

Johanna Gottschamel ◽

Andreas Lössl ◽

Stephanie Ruf ◽

Yanliang Wang ◽

Morten Skaugen ◽

...

Keyword(s):

Dengue Virus ◽

Envelope Protein ◽

Constitutive Expression ◽

Protein Domain ◽

Expression Systems ◽

Virus Envelope ◽

Virus Envelope Protein ◽

Domain Iii

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Exposure of Platelets to Dengue Virus and Envelope Protein Domain III Induces Nlrp3 Inflammasome-Dependent Platelet Cell Death and Thrombocytopenia in Mice

Frontiers in Immunology ◽

10.3389/fimmu.2021.616394 ◽

2021 ◽

Vol 12 ◽

Author(s):

Te-Sheng Lien ◽

Hao Chan ◽

Der-Shan Sun ◽

Jhen-Cheng Wu ◽

You-Yen Lin ◽

...

Keyword(s):

Cell Death ◽

Dengue Virus ◽

Platelet Activation ◽

Nlrp3 Inflammasome ◽

Envelope Protein ◽

Competitive Inhibitor ◽

Protein Domain ◽

Severe Dengue ◽

Platelet Signaling ◽

Domain Iii

In tropical and subtropical regions, mosquito-borne dengue virus (DENV) infections can lead to severe dengue, also known as dengue hemorrhage fever, which causes bleeding, thrombocytopenia, and blood plasma leakage and increases mortality. Although DENV-induced platelet cell death was linked to disease severity, the role of responsible viral factors and the elicitation mechanism of abnormal platelet activation and cell death remain unclear. DENV and virion-surface envelope protein domain III (EIII), a cellular binding moiety of the virus particle, highly increase during the viremia stage. Our previous report suggested that exposure to such viremia EIII levels can lead to cell death of endothelial cells, neutrophils, and megakaryocytes. Here we found that both DENV and EIII could induce abnormal platelet activation and predominantly necrotic cell death pyroptosis. Blockages of EIII-induced platelet signaling using the competitive inhibitor chondroitin sulfate B or selective Nlrp3 inflammasome inhibitors OLT1177 and Z-WHED-FMK markedly ameliorated DENV- and EIII-induced thrombocytopenia, platelet activation, and cell death. These results suggest that EIII could be considered as a virulence factor of DENV, and that Nlrp3 inflammasome is a feasible target for developing therapeutic approaches against dengue-induced platelet defects.

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