{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T07:54:12Z","timestamp":1781682852259,"version":"3.54.5"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Amazon Foundation for the Support of Studies and Research","award":["00000.9.000533\/2023"],"award-info":[{"award-number":["00000.9.000533\/2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Dengue is an arboviral disease of global significance caused by Orthoflavivirus denguei (DENV), which has four antigenically distinct serotypes. The envelope (E) protein plays a critical role in viral entry and eliciting immune responses. This study aimed to compare the biochemical and immunological properties of the E protein across the four DENV serotypes using in silico approaches. E protein reference sequences were retrieved from RefSeq and analyzed with various bioinformatics tools. Sequence alignment revealed identities ranging from 63.08% to 77.69%. Biochemical analysis showed minimal variation in molecular weight and isoelectric point; however, the net charge of DENV-3 E protein was notably lower. Secondary structure predictions indicated a predominance of alpha-helices in DENVs-1\/2, while DENVs-3\/4 featured more beta-sheets. Post-translational modification analysis revealed mostly casein kinase II phosphorylation sites across all serotypes, with DENV-4 uniquely presenting also tyrosine kinase sites. Amino acids W231\/D341 in DENV-1, Q86 in DENVs-2\/4, and D87\/D339 in DENV-3 showed maximum antigenicity scores in B cell recognition, while the human leukocyte antigen (HLA) alleles B*08:01\/B*39:01 and DRB4*01:01, recognized by T cells, presented the highest number of predicted epitopes for the different DENV serotypes. Conservation analysis showed that the major antigenic regions highlighted in this study are highly conserved among contemporary DENV isolates despite the genetic variability observed within each serotype. These findings suggest that subtle structural differences in the E protein may contribute to distinct immunogenic profiles, highlighting candidate regions for future investigation.<\/jats:p>","DOI":"10.3390\/cimb48060631","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:56:31Z","timestamp":1781675791000},"page":"631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serotype-Specific Biochemical and Immunological Signatures of Dengue Virus Envelope Proteins"],"prefix":"10.3390","volume":"48","author":[{"given":"Iasmin V.","family":"Costa","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Biological and Health Sciences, University of Par\u00e1 State, Bel\u00e9m 66095-662, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4607-9346","authenticated-orcid":false,"given":"Ana Cec\u00edlia R.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Section for Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ananindeua 67030-000, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6615-1387","authenticated-orcid":false,"given":"Carlos Alberto M.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Biological and Health Sciences, University of Par\u00e1 State, Bel\u00e9m 66095-662, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Harapan, H., Michie, A., Sasmono, R.T., and Imrie, A. (2020). Dengue: A Minireview. Viruses, 12.","DOI":"10.3390\/v12080829"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1139\/cjm-2020-0572","article-title":"Dengue virus: Epidemiology, biology, and disease aetiology","volume":"67","author":"Roy","year":"2021","journal-title":"Can. J. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1002\/jmv.25646","article-title":"Dengue proteins with their role in pathogenesis, and strategies for developing an effective anti-dengue treatment: A review","volume":"92","author":"Nasar","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e01345","DOI":"10.1002\/adts.202501345","article-title":"Computational Modeling of the Dengue Virus Envelope and Membrane Protein Complex Maturation Pathway","volume":"9","author":"Chaudhuri","year":"2026","journal-title":"Adv. Theory Simul."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1504\/IJBRA.2010.037989","article-title":"Prediction of the post-translational modification sites on dengue virus E protein and deciphering their role in pathogenesis","volume":"6","author":"Mahbub","year":"2010","journal-title":"Int. J. Bioinform. Res. Appl."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ullah, H., Ullah, S., Li, J., Yang, F., and Tan, L. (2024). An In Silico Design of a Vaccine Against All Serotypes of the Dengue Virus Based on Virtual Screening of B-Cell and T-Cell Epitopes. Biology, 13.","DOI":"10.20944\/preprints202407.0023.v1"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"D243","DOI":"10.1093\/nar\/gkae1038","article-title":"NCBI RefSeq: Reference sequence standards through 25 years of curation and annotation","volume":"53","author":"Goldfarb","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"W521","DOI":"10.1093\/nar\/gkae241","article-title":"The EMBL-EBI Job Dispatcher sequence analysis tools framework in 2024","volume":"52","author":"Madeira","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/msb.2011.75","article-title":"Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega","volume":"7","author":"Sievers","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1126\/science.1604319","article-title":"Exhaustive matching of the entire protein sequence database","volume":"256","author":"Gonnet","year":"1992","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0968-0004(99)01540-6","article-title":"NPS@: Network protein sequence analysis","volume":"25","author":"Combet","year":"2000","journal-title":"Trends Biochem. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5425","DOI":"10.1021\/bi00367a013","article-title":"New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: Correlation of predicted surface residues with antigenicity and X-ray-derived accessible sites","volume":"25","author":"Parker","year":"1986","journal-title":"Biochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","article-title":"NetMHCpan-4.1 and NetMHCIIpan-4.0: Improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data","volume":"48","author":"Reynisson","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jim.2015.03.022","article-title":"Development and validation of a broad scheme for prediction of HLA class II restricted T cell epitopes","volume":"422","author":"Paul","year":"2015","journal-title":"J. Immunol. Methods."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Soto, L.F., Requena, D., and Fuxman Bass, J.I. (2022). Epitope-Evaluator: An interactive web application to study predicted T-cell epitopes. PLoS ONE, 17.","DOI":"10.1101\/2022.05.09.491119"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D56","DOI":"10.1093\/nar\/gkae1114","article-title":"GenBank 2025 update","volume":"53","author":"Sayers","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sarker, A., Dhama, N., and Gupta, R.D. (2023). Dengue virus neutralizing antibody: A review of targets, cross-reactivity, and antibody-dependent enhancement. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1200195"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"199018","DOI":"10.1016\/j.virusres.2022.199018","article-title":"Dengue virus infection\u2014A review of pathogenesis, vaccines, diagnosis and therapy","volume":"324","author":"Kok","year":"2023","journal-title":"Virus Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.cell.2018.02.054","article-title":"Common Features of Enveloped Viruses and Implications for Immunogen Design for Next-Generation Vaccines","volume":"172","author":"Rey","year":"2018","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.virol.2005.09.036","article-title":"Class II virus membrane fusion proteins","volume":"344","author":"Kielian","year":"2006","journal-title":"Virology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1146\/annurev-cellbio-101512-122422","article-title":"Virus and cell fusion mechanisms","volume":"30","author":"Podbilewicz","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Anwar, A., Hosoya, T., Leong, K.M., Onogi, H., Okuno, Y., Hiramatsu, T., Koyama, H., Suzuki, M., Hagiwara, M., and Garcia-Blanco, M.A. (2011). The kinase inhibitor SFV785 dislocates dengue virus envelope protein from the replication complex and blocks virus assembly. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023246"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.3389\/fmicb.2017.01415","article-title":"Dengue Virus Glycosylation: What Do We Know?","volume":"8","author":"Yap","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21857","DOI":"10.1074\/jbc.M115.666859","article-title":"Hepatitis C Virus Particle Assembly Involves Phosphorylation of NS5A by the c-Abl Tyrosine Kinase","volume":"290","author":"Yamauchi","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Stewart, C.M., Phan, A., Bo, Y., LeBlond, N.D., Smith, T.K.T., Laroche, G., Gigu\u00e8re, P.M., Fullerton, M.D., Pelchat, M., and Kobasa, D. (2021). Ebola virus triggers receptor tyrosine kinase-dependent signaling to promote the delivery of viral particles to entry-conducive intracellular compartments. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009275"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1007\/s00253-018-8822-y","article-title":"Dengue viruses and promising envelope protein domain III-based vaccines","volume":"102","author":"Fahimi","year":"2018","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Appanna, R., Ponnampalavanar, S., Lum Chai See, L., and Sekaran, S.D. (2010). Susceptible and protective HLA class 1 alleles against dengue fever and dengue hemorrhagic fever patients in a Malaysian population. PLoS ONE, 5, Erratum in PLoS ONE 2011, 6, 972cc8f0-5c9e-4d74-b98b-217a2f80a4bd.","DOI":"10.1371\/journal.pone.0013029"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rathakrishnan, A., Klekamp, B., Wang, S.M., Komarasamy, T.V., Natkunam, S.K., Sathar, J., Azizan, A., Sanchez-Anguiano, A., Manikam, R., and Sekaran, S.D. (2014). Clinical and immunological markers of dengue progression in a study cohort from a hyperendemic area in Malaysia. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092021"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1089\/vim.2018.0151","article-title":"HLA-A, -B, -DRB1 Alleles as Genetic Predictive Factors for Dengue Disease: A Systematic Review and Meta-Analysis","volume":"32","author":"Chen","year":"2019","journal-title":"Viral Immunol."},{"key":"ref_31","first-page":"e31485","article-title":"Major Histocompatibility Complex Class I and Dengue Hemorrhagic Fever: A Meta-Analysis of Human Leukocyte Antigens A*24 and B*44","volume":"14","author":"Cook","year":"2022","journal-title":"Cureus"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1590\/S0074-02762012000200012","article-title":"HLA-A*01 allele: A risk factor for dengue haemorrhagic fever in Brazil\u2019s population","volume":"107","author":"Monteiro","year":"2012","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.humimm.2007.03.001","article-title":"HLA-A, -B, -C, and -DRB1 allele frequencies in Cuban individuals with antecedents of dengue 2 disease: Advantages of the Cuban population for HLA studies of dengue virus infection","volume":"68","author":"Sierra","year":"2007","journal-title":"Hum. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.humimm.2013.01.027","article-title":"Association of HLA-DRB1 and TNF genotypes with dengue hemorrhagic fever","volume":"74","author":"Alagarasu","year":"2013","journal-title":"Hum. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Grifoni, A., Moore, E., Voic, H., Sidney, J., Phillips, E., Jadi, R., Mallal, S., De Silva, A.D., De Silva, A.M., and Peters, B. (2019). Characterization of Magnitude and Antigen Specificity of HLA-DP, DQ, and DRB3\/4\/5 Restricted DENV-Specific CD4+ T Cell Responses. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01568"},{"key":"ref_36","first-page":"99","article-title":"HLA and other gene associations with dengue disease severity","volume":"338","author":"Stephens","year":"2010","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ghosh, A., Mondal, S., Sadhukhan, S., and Sadhukhan, P.C. (2025). Dengue Virus and the Host Immune System: A Battle of Immune Modulation, Response and Evasion. Pathogens, 14.","DOI":"10.3390\/pathogens14111132"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/6\/631\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T07:18:06Z","timestamp":1781680686000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/6\/631"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["cimb48060631"],"URL":"https:\/\/doi.org\/10.3390\/cimb48060631","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]}}}