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Severe dengue presentations are characterized by vascular leakage, hemorrhagic manifestations, and shock, which can lead to multiorgan failure. Recent studies highlight the crucial role of extracellular vesicles (EVs) in the pathogenesis of dengue, influencing immune response and disease progression. EVs, nanometric structures secreted by cells, mediate viral dissemination, immune modulation, and endothelial dysfunction by transporting biomolecules such as microRNAs (miRNAs) and viral proteins. Infected cell-derived EVs carry viral components, including NS protein and miRNAs like miR-21 and miR-126-5p, which compromise endothelial integrity and activate immune pathways such as Toll-like receptor, NF-\u03baB, and JAK-STAT signaling. This, together with the immune response, leads to the release of pro-inflammatory cytokines, including TNF-\u03b1, IL-1\u03b2, IL-6, and IFN-\u03b3. EVs also facilitate viral immune evasion by suppressing antiviral responses. Recent analyses of miRNAs within EVs suggest their potential as biomarkers for disease progression. Differentially expressed miRNAs in circulating EVs correlate with severe outcomes, providing tools for risk stratification and therapeutic monitoring. Advanced techniques, such as nanoparticle tracking analysis and flow cytometry, allow precise EV characterization, supporting their integration into clinical applications.<\/jats:p>","DOI":"10.3390\/v17060807","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T12:27:09Z","timestamp":1748867229000},"page":"807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Role of Extracellular Vesicles in Severe Dengue: Virus\u2013Host Interactions and Biomarker Potential"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4123-6741","authenticated-orcid":false,"given":"Juan Sebastian Henao","family":"Agudelo","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, Central Unit of Valle del Cauca (UCEVA), Tulua 763022, Valle del Cauca, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7836-4280","authenticated-orcid":false,"given":"Gabriel","family":"Pereira","sequence":"additional","affiliation":[{"name":"School of Medicine, Nephrology Division, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04021-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9lio Junior da Costa","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Pharmacology, Institute of Biosciences, Universidade Estadual Paulista \u201cJ\u00falio de Mesquita Filho\u201d (UNESP), Botucatu 18610-307, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Murugesan, A., and Manoharan, M. (2020). Dengue Virus. Emerging and Reemerging Viral Pathogens, Elsevier.","DOI":"10.1016\/B978-0-12-819400-3.00016-8"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.envres.2016.07.026","article-title":"Dengue in a Changing Climate","volume":"151","author":"Ebi","year":"2016","journal-title":"Environ. Res."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"e2034","DOI":"10.1002\/hsr2.2034","article-title":"Upsurge of Dengue Outbreaks in Several WHO Regions: Public Awareness, Vector Control Activities, and International Collaborations Are Key to Prevent Spread","volume":"7","author":"Sarker","year":"2024","journal-title":"Health Sci. Rep."},{"key":"ref_5","unstructured":"(2024, December 31). Dengue Multi-Country Grade 3 Outbreak 2024\u2014PAHO\/WHO|Pan American Health Organization. Available online: https:\/\/www.paho.org\/en\/topics\/dengue\/dengue-multi-country-grade-3-outbreak."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.7861\/clinmed.2021-0791","article-title":"Dengue Infection: Global Importance, Immunopathology and Management","volume":"22","author":"Kularatne","year":"2022","journal-title":"Clin. Med."},{"key":"ref_7","first-page":"e46713","article-title":"Updates in the Management of Dengue Shock Syndrome: A Comprehensive Review","volume":"15","author":"Singh","year":"2023","journal-title":"Cureus"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00284-020-02284-w","article-title":"Current Understanding of the Pathogenesis of Dengue Virus Infection","volume":"78","author":"Bhatt","year":"2021","journal-title":"Curr. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/imm.12748","article-title":"Pathogenesis of Vascular Leak in Dengue Virus Infection","volume":"151","author":"Malavige","year":"2017","journal-title":"Immunology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1080\/22221751.2019.1685913","article-title":"Dengue Haemorrhagic Fever: A Job Done via Exosomes?","volume":"8","author":"Mishra","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma Powers Differential Expression Analyses for RNA-Sequencing and Microarray Studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_13","unstructured":"R Core Team (2023). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"W154","DOI":"10.1093\/nar\/gkad431","article-title":"DIANA-miRPath v4.0: Expanding Target-Based miRNA Functional Analysis in Cell-Type and Tissue Contexts","volume":"51","author":"Tastsoglou","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_15","first-page":"217","article-title":"Genomics, Proteomics and Evolution of Dengue Virus","volume":"16","author":"Dwivedi","year":"2017","journal-title":"Brief. Funct. Genom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16055","DOI":"10.1038\/nrdp.2016.55","article-title":"Dengue Infection","volume":"2","author":"Guzman","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.hgmx.2016.09.011","article-title":"Clinical and Differential Diagnosis: Dengue, Chikungunya and Zika","volume":"81","year":"2018","journal-title":"Rev. M\u00e9dica Hosp. Gen. M\u00e9xico"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jointm.2023.07.007","article-title":"Severe Dengue in the Intensive Care Unit","volume":"4","author":"Tejo","year":"2024","journal-title":"J. Intensiv. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3201\/eid2901.220838","article-title":"Burden of Postinfectious Symptoms after Acute Dengue, Vietnam","volume":"29","author":"Tam","year":"2023","journal-title":"Emerg. Infect. Dis."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41577-019-0123-x","article-title":"Adaptive Immune Responses to Primary and Secondary Dengue Virus Infections","volume":"19","author":"Rathore","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lee, M.F., Voon, G.Z., Lim, H.X., Chua, M.L., and Poh, C.L. (2022). Innate and Adaptive Immune Evasion by Dengue Virus. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.1004608"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Latanova, A., Karpov, V., and Starodubova, E. (2024). Extracellular Vesicles in Flaviviridae Pathogenesis: Their Roles in Viral Transmission, Immune Evasion, and Inflammation. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042144"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12964-023-01103-6","article-title":"A Review of the Regulatory Mechanisms of Extracellular Vesicles-Mediated Intercellular Communication","volume":"21","author":"Liu","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Aloi, N., Drago, G., Ruggieri, S., Cibella, F., Colombo, P., and Longo, V. (2024). Extracellular Vesicles and Immunity: At the Crossroads of Cell Communication. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021205"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s12964-021-00787-y","article-title":"Extracellular Vesicles: Mediators of Intercellular Communication in Tissue Injury and Disease","volume":"19","author":"Bunn","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12020-012-9839-0","article-title":"Extracellular Vesicles as an Emerging Mechanism of Cell-to-Cell Communication","volume":"44","author":"Tetta","year":"2013","journal-title":"Endocrine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A Review of Programmed Cell Death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"107307","DOI":"10.1016\/j.phrs.2024.107307","article-title":"Extracellular Vesicles Meet Mitochondria: Potential Roles in Regenerative Medicine","volume":"206","author":"Wu","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yu, L., Zhu, G., Zhang, Z., Yu, Y., Zeng, L., Xu, Z., Weng, J., Xia, J., Li, J., and Pathak, J.L. (2023). Apoptotic Bodies: Bioactive Treasure Left behind by the Dying Cells with Robust Diagnostic and Therapeutic Application Potentials. J. Nanobiotechnology, 21.","DOI":"10.1186\/s12951-023-01969-1"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.coi.2019.11.009","article-title":"Flippase and Scramblase for Phosphatidylserine Exposure","volume":"62","author":"Nagata","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1096\/fba.2020-00127","article-title":"The Ins and Outs of Microvesicles","volume":"3","author":"Clancy","year":"2021","journal-title":"FASEB Bioadv."},{"key":"ref_33","first-page":"1877","article-title":"Rho-Rho Kinase Pathway in the Actomyosin Contraction and Cell-Matrix Adhesion in Immortalized Human Trabecular Meshwork Cells","volume":"17","author":"Ramachandran","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1161\/01.RES.0000090998.08629.60","article-title":"Ca2+-Dependent Activation of Rho and Rho Kinase in Membrane Depolarization-Induced and Receptor Stimulation-Induced Vascular Smooth Muscle Contraction","volume":"93","author":"Sakurada","year":"2003","journal-title":"Circ. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.devcel.2023.01.006","article-title":"GPR143 Controls ESCRT-Dependent Exosome Biogenesis and Promotes Cancer Metastasis","volume":"58","author":"Lee","year":"2023","journal-title":"Dev. Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/ncb2000","article-title":"Rab27a and Rab27b Control Different Steps of the Exosome Secretion Pathway","volume":"12","author":"Ostrowski","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.semcancer.2014.04.009","article-title":"Sorting It out: Regulation of Exosome Loading","volume":"28","author":"Baixauli","year":"2014","journal-title":"Semin. Cancer Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41392-024-01735-1","article-title":"Extracellular Vesicles as Tools and Targets in Therapy for Diseases","volume":"9","author":"Kumar","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yoshikawa, F.S.Y., Teixeira, F.M.E., Sato, M.N., and da Oliveira, L.M.S. (2019). Delivery of microRNAs by Extracellular Vesicles in Viral Infections: Could the News Be Packaged?. Cells, 8.","DOI":"10.3390\/cells8060611"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"100049","DOI":"10.1016\/j.vesic.2024.100049","article-title":"Role of Extracellular Vesicle microRNAs and RNA Binding Proteins on Glioblastoma Dynamics and Therapeutics Development","volume":"4","author":"Singh","year":"2024","journal-title":"Extracell. Vesicle"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Safadi, D.E., Lebeau, G., Lagrave, A., M\u00e9lade, J., Grondin, L., Rosanaly, S., Begue, F., Hoareau, M., Veeren, B., and Roche, M. (2023). Extracellular Vesicles Are Conveyors of the NS1 Toxin during Dengue Virus and Zika Virus Infection. Viruses, 15.","DOI":"10.3390\/v15020364"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Su, Y., Lin, T., Liu, C., Cheng, C., Han, X., and Jiang, X. (2021). microRNAs, the Link Between Dengue Virus and the Host Genome. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.714409"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Wong, R.R., Abd-Aziz, N., Affendi, S., and Poh, C.L. (2020). Role of microRNAs in Antiviral Responses to Dengue Infection. J. Biomed. Sci., 27.","DOI":"10.1186\/s12929-019-0614-x"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.antiviral.2017.03.020","article-title":"miR-21 Promotes Dengue Virus Serotype 2 Replication in HepG2 Cells","volume":"142","author":"Kanokudom","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Fu, Y., Zhang, L., Zhang, F., Tang, T., Zhou, Q., Feng, C., Jin, Y., and Wu, Z. (2017). Exosome-Mediated miR-146a Transfer Suppresses Type I Interferon Response and Facilitates EV71 Infection. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006611"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00705-023-05744-3","article-title":"Roles and Mechanisms of Exosomal microRNAs in Viral Infections","volume":"168","author":"Mao","year":"2023","journal-title":"Arch. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"de Martins, S.T., Kuczera, D., L\u00f6tvall, J., Bordignon, J., and Alves, L.R. (2018). Characterization of Dendritic Cell-Derived Extracellular Vesicles During Dengue Virus Infection. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01792"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Sorop, A., Iacob, R., Iacob, S., Constantinescu, D., Chitoiu, L., Fertig, T.E., Dinischiotu, A., Chivu-Economescu, M., Bacalbasa, N., and Savu, L. (2020). Plasma Small Extracellular Vesicles Derived miR-21-5p and miR-92a-3p as Potential Biomarkers for Hepatocellular Carcinoma Screening. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00712"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1080\/20477724.2022.2088465","article-title":"The Expression of Circulating Hsa-miR-126-3p in Dengue-Infected Thai Pediatric Patients","volume":"117","author":"Sriprapun","year":"2023","journal-title":"Pathog. Glob. Health"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"509306","DOI":"10.1155\/2015\/509306","article-title":"Dengue Virus-Induced Inflammation of the Endothelium and the Potential Roles of Sphingosine Kinase-1 and MicroRNAs","volume":"2015","author":"Aloia","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Cloherty, A.P.M., Rader, A.G., Patel, K.S., Eisden, T.-J.T.H.D., van Piggelen, S., Schreurs, R.R.C.E., and Ribeiro, C.M.S. (2024). Dengue Virus Exploits Autophagy Vesicles and Secretory Pathways to Promote Transmission by Human Dendritic Cells. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1260439"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Wu, X., Niu, J., and Shi, Y. (2024). Exosomes Target HBV-Host Interactions to Remodel the Hepatic Immune Microenvironment. J. Nanobiotechnology, 22.","DOI":"10.1186\/s12951-024-02544-y"},{"key":"ref_53","unstructured":"MacLachlan, N.J., and Dubovi, E.J. (2011). Chapter 3\u2014Pathogenesis of Viral Infections and Diseases. Fenner\u2019s Veterinary Virology, Academic Press. [4th ed.]."},{"key":"ref_54","unstructured":"Klasse, P.J. (2015). The Molecular Basis of Viral Infection, Academic Press."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1099\/vir.0.032060-0","article-title":"The NS1 Protein of Influenza A Virus Suppresses Interferon-Regulated Activation of Antigen-Presentation and Immune-Proteasome Pathways","volume":"92","author":"Tisoncik","year":"2011","journal-title":"J. Gen. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Caobi, A., Nair, M., and Raymond, A.D. (2020). Extracellular Vesicles in the Pathogenesis of Viral Infections in Humans. Viruses, 12.","DOI":"10.3390\/v12101200"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/boc.201400081","article-title":"Immunomodulatory Role of microRNAs Transferred by Extracellular Vesicles","volume":"107","year":"2015","journal-title":"Biol. Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1074\/jbc.M116.769893","article-title":"Extracellular MicroRNA Signature of Human Helper T Cell Subsets in Health and Autoimmunity","volume":"292","author":"Torri","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Nail, H.M., Chiu, C.-C., Leung, C.-H., Ahmed, M.M.M., and Wang, H.-M.D. (2023). Exosomal miRNA-Mediated Intercellular Communications and Immunomodulatory Effects in Tumor Microenvironments. J. Biomed. Sci., 30.","DOI":"10.1186\/s12929-023-00964-w"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Wang, S., Sun, J., Dastgheyb, R.M., and Li, Z. (2022). Tumor-Derived Extracellular Vesicles Modulate Innate Immune Responses to Affect Tumor Progression. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1045624"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1080\/09537104.2020.1755031","article-title":"A New Player in the Game: Platelet-Derived Extracellular Vesicles in Dengue Hemorrhagic Fever","volume":"31","year":"2020","journal-title":"Platelets"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Vedpathak, S., Sharma, A., Palkar, S., Bhatt, V.R., Patil, V.C., Kakrani, A.L., Mishra, A., Bhosle, D., Arankalle, V.A., and Shrivastava, S. (2024). Platelet Derived Exosomes Disrupt Endothelial Cell Monolayer Integrity and Enhance Vascular Inflammation in Dengue Patients. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1285162"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e28614","DOI":"10.1002\/jmv.28614","article-title":"Association of Exosomal miR-96-5p and miR-146a-5p with the Disease Severity in Dengue Virus Infection","volume":"95","author":"Pradhan","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e01823-23","DOI":"10.1128\/mbio.01823-23","article-title":"Extracellular Vesicles Recovered from Plasma of Severe Dengue Patients Induce CD4+ T Cell Suppression through PD-L1\/PD-1 Interaction","volume":"14","author":"Kumari","year":"2023","journal-title":"mBio"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.4049\/jimmunol.2000411","article-title":"Dengue Virus Degrades USP33\u2013ATF3 Axis via Extracellular Vesicles to Activate Human Microglial Cells","volume":"205","author":"Mishra","year":"2020","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Gold, A.S., Feitosa-Suntheimer, F., Araujo, R.V., Hekman, R.M., Asad, S., Londono-Renteria, B., Emili, A., and Colpitts, T.M. (2020). Dengue Virus Infection of Aedes Aegypti Alters Extracellular Vesicle Protein Cargo to Enhance Virus Transmission. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186609"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1086\/599795","article-title":"Dengue Virus Infection Differentially Regulates Endothelial Barrier Function over Time through Type I Interferon Effects","volume":"200","author":"Liu","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nrcardio.2014.40","article-title":"Cardiovascular Manifestations of the Emerging Dengue Pandemic","volume":"11","author":"Yacoub","year":"2014","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.antiviral.2014.07.005","article-title":"Endothelial Cells in Dengue Hemorrhagic Fever","volume":"109","author":"Srikiatkhachorn","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"H1181","DOI":"10.1152\/ajpheart.00579.2020","article-title":"Extracellular Vesicles: New Players in Regulating Vascular Barrier Function","volume":"319","author":"Chatterjee","year":"2020","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"107309","DOI":"10.1016\/j.phrs.2024.107309","article-title":"Insight into Endothelial Cell-Derived Extracellular Vesicles in Cardiovascular Disease: Molecular Mechanisms and Clinical Implications","volume":"207","author":"Wang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.reth.2024.09.016","article-title":"Promising Nanotherapeutics of Stem Cell Extracellular Vesicles in Liver Regeneration","volume":"26","author":"Guo","year":"2024","journal-title":"Regen. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"171774","DOI":"10.1016\/j.scitotenv.2024.171774","article-title":"Environmental Pollutants and Exosomes: A New Paradigm in Environmental Health and Disease","volume":"925","author":"Salahshoori","year":"2024","journal-title":"Sci. Total. Environ."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41420-021-00670-2","article-title":"MicroRNA in Extracellular Vesicles Regulates Inflammation through Macrophages under Hypoxia","volume":"7","author":"Li","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1191\/1358863x03vm466oa","article-title":"High Circulating Levels of Cytokines (IL-6 and TNFalpha), Adhesion Molecules (VCAM-1 and ICAM-1) and Selectins in Patients with Peripheral Arterial Disease at Rest and after a Treadmill Test","volume":"8","author":"Signorelli","year":"2003","journal-title":"Vasc. Med."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Chiaradia, E., Tancini, B., Emiliani, C., Delo, F., Pellegrino, R.M., Tognoloni, A., Urbanelli, L., and Buratta, S. (2021). Extracellular Vesicles under Oxidative Stress Conditions: Biological Properties and Physiological Roles. Cells, 10.","DOI":"10.3390\/cells10071763"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Tang, F., Zhao, X.-L., Xu, L.-Y., Zhang, J.-N., Ao, H., and Peng, C. (2024). Endothelial Dysfunction: Pathophysiology and Therapeutic Targets for Sepsis-Induced Multiple Organ Dysfunction Syndrome. Biomed. Pharmacother., 178.","DOI":"10.1016\/j.biopha.2024.117180"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Meuren, L.M., Prestes, E.B., Papa, M.P., de Carvalho, L.R.P., Mustaf\u00e1, Y.M., da Costa, L.S., Da Poian, A.T., Bozza, M.T., and Arruda, L.B. (2022). Infection of Endothelial Cells by Dengue Virus Induces ROS Production by Different Sources Affecting Virus Replication, Cellular Activation, Death and Vascular Permeability. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.810376"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e01551-20","DOI":"10.1128\/JVI.01551-20","article-title":"Dengue Virus Targets Nrf2 for NS2B3-Mediated Degradation Leading to Enhanced Oxidative Stress and Viral Replication","volume":"94","author":"Ferrari","year":"2020","journal-title":"J. Virol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Park, J.-S., Rustamov, N., and Roh, Y.-S. (2023). The Roles of NFR2-Regulated Oxidative Stress and Mitochondrial Quality Control in Chronic Liver Diseases. Antioxidants, 12.","DOI":"10.3390\/antiox12111928"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Auber, M., and Svenningsen, P. (2022). An Estimate of Extracellular Vesicle Secretion Rates of Human Blood Cells. J. Extracell. Biol., 1.","DOI":"10.1002\/jex2.46"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Limothai, U., Jantarangsi, N., Suphavejkornkij, N., Tachaboon, S., Dinhuzen, J., Chaisuriyong, W., Trongkamolchai, S., Wanpaisitkul, M., Chulapornsiri, C., and Tiawilai, A. (2022). Discovery and Validation of Circulating miRNAs for the Clinical Prognosis of Severe Dengue. PLoS Neglected Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0010836"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"195","DOI":"10.7150\/ijms.13996","article-title":"Dysregulated Serum MiRNA Profile and Promising Biomarkers in Dengue-Infected Patients","volume":"13","author":"Ouyang","year":"2016","journal-title":"Int. J. Med. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1177\/0004563215604001","article-title":"microRNA Expression in Blood of Dengue Patients","volume":"53","author":"Tambyah","year":"2016","journal-title":"Ann. Clin. Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Hapugaswatta, H., Amarasena, P., Premaratna, R., Seneviratne, K.N., and Jayathilaka, N. (2020). Differential Expression of microRNA, miR-150 and Enhancer of Zeste Homolog 2 (EZH2) in Peripheral Blood Cells as Early Prognostic Markers of Severe Forms of Dengue. J. Biomed. Sci., 27.","DOI":"10.1186\/s12929-020-0620-z"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/MOH.0000000000000424","article-title":"MicroRNAs in Endothelial Cell Homeostasis and Vascular Disease","volume":"25","year":"2018","journal-title":"Curr. Opin. Hematol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e009244","DOI":"10.1161\/JAHA.118.009244","article-title":"Inhibition of MicroRNA-155 Supports Endothelial Tight Junction Integrity Following Oxygen-Glucose Deprivation","volume":"7","author":"Gardiner","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1128\/JVI.02207-14","article-title":"Microparticles Provide a Novel Biomarker to Predict Severe Clinical Outcomes of Dengue Virus Infection","volume":"89","author":"Punyadee","year":"2015","journal-title":"J. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e1376153","DOI":"10.1080\/2162402X.2017.1376153","article-title":"Elevated Levels of Extracellular Vesicles Are Associated with Therapy Failure and Disease Progression in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy","volume":"7","author":"Bittner","year":"2018","journal-title":"OncoImmunology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e24099","DOI":"10.1016\/j.heliyon.2024.e24099","article-title":"Classical Monocytes-Low Expressing HLA-DR Is Associated with Higher Mortality Rate in SARS-CoV-2+ Young Patients with Severe Pneumonia","volume":"10","author":"Ayala","year":"2024","journal-title":"Heliyon"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e12385","DOI":"10.1002\/jev2.12385","article-title":"MIBlood-EV: Minimal Information to Enhance the Quality and Reproducibility of Blood Extracellular Vesicle Research","volume":"12","author":"Lucien","year":"2023","journal-title":"J. Extracell. Vesicles"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal Information for Studies of Extracellular Vesicles (MISEV2023): From Basic to Advanced Approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Kowkabany, G., and Bao, Y. (2024). Nanoparticle Tracking Analysis: An Effective Tool to Characterize Extracellular Vesicles. Molecules, 29.","DOI":"10.3390\/molecules29194672"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.ijid.2023.07.010","article-title":"Global Prevalence of Asymptomatic Dengue Infections\u2014A Systematic Review and Meta-Analysis","volume":"134","author":"Asish","year":"2023","journal-title":"Int. J. Infect. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1002\/cyto.a.23782","article-title":"FCMPASS Software Aids Extracellular Vesicle Light Scatter Standardization","volume":"97","author":"Welsh","year":"2020","journal-title":"Cytom. A"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Chen, H.-R., Chuang, Y.-C., Lin, Y.-S., Liu, H.-S., Liu, C.-C., Perng, G.-C., and Yeh, T.-M. (2016). Dengue Virus Nonstructural Protein 1 Induces Vascular Leakage through Macrophage Migration Inhibitory Factor and Autophagy. PLoS Neglected Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004828"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12985-018-0970-2","article-title":"Dengue Virus-like Particles Mimic the Antigenic Properties of the Infectious Dengue Virus Envelope","volume":"15","author":"Metz","year":"2018","journal-title":"Virol. J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e00724-20","DOI":"10.1128\/mSystems.00724-20","article-title":"High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression","volume":"5","author":"Saini","year":"2020","journal-title":"mSystems"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1002\/iub.2275","article-title":"How Hypoxia Regulate Exosomes in Ischemic Diseases and Cancer Microenvironment?","volume":"72","author":"Yaghoubi","year":"2020","journal-title":"IUBMB Life"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.15252\/embj.201695642","article-title":"Hypoxia Enhances Antibody-dependent Dengue Virus Infection","volume":"36","author":"Gan","year":"2017","journal-title":"EMBO J."},{"key":"ref_101","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_102","doi-asserted-by":"crossref","unstructured":"Sahin, M., Remy, M.M., Merkler, D., and Pinschewer, D.D. (2021). The Janus Kinase Inhibitor Ruxolitinib Prevents Terminal Shock in a Mouse Model of Arenavirus Hemorrhagic Fever. Microorganisms, 9.","DOI":"10.3390\/microorganisms9030564"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2018.07.022","article-title":"Synergism Between the Tyrosine Kinase Inhibitor Sunitinib and Anti-TNF Antibody Protects Against Lethal Dengue Infection","volume":"158","author":"Branche","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00281-017-0625-1","article-title":"Immune-Mediated Cytokine Storm and Its Role in Severe Dengue","volume":"39","author":"Srikiatkhachorn","year":"2017","journal-title":"Semin. Immunopathol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/6\/807\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:44:54Z","timestamp":1760031894000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/6\/807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,31]]},"references-count":104,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["v17060807"],"URL":"https:\/\/doi.org\/10.3390\/v17060807","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,31]]}}}