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Background: Dengue virus (DENV) is described as the most prevalent arbovirus, infecting at least 50. million people worldwide. During infection, an intricate network of cytokines, a group of substances closely related to disease s...
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Background: Dengue virus (DENV) is described as the most prevalent arbovirus, infecting at least 50. million people worldwide. During infection, an intricate network of cytokines, a group of substances closely related to disease severity, is released. Recently, it was observed that both DENV-infected epithelial cells undergoing necrosis and dendritic cells (DCs) are able to release a non-classical pro-inflammatory cytokine called high mobility group box 1 (HMGB1). Objectives: The aim of this study was to evaluate whether HMGB1 levels were altered in DENV-infected patients' sera and whether this augment correlated with disease pathogenesis. Study design: Samples from DENV-infected patients were collected from different days after the onset of symptoms and from patients experiencing primary or secondary infection. The circulating HMGB1 concentration was measured in healthy blood donors as well as in donors with primary and secondary cases of DENV infection by a quantitative capture ELISA assay. Results: We observed that the HMGB1 concentration in DENV-infected patients was significantly higher than in healthy patients. HMGB1 levels reached the highest concentration in the first day after the onset of symptoms and decreased throughout the course of the infection. Moreover, we observed that the HMGB1 concentration was augmented during secondary infection as well. Conclusion: We hypothesize that HMGB1 levels correlate with disease pathogenesis, specifically with the clinical symptoms and secondary infection, implicating a pro-inflammatory cytokine role for HMGB1 in DENV infection. This is the first report assessing the circulating levels of HMGB1 during DENV infection.
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Abstract Exosomes are small extracellular vesicles secreted by cells and have a major role in cell‐to‐cell signaling. As dengue infection progresses from a mild to a severe form of infection, the exosome's microRNA (miRNA) compo...
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Abstract Exosomes are small extracellular vesicles secreted by cells and have a major role in cell‐to‐cell signaling. As dengue infection progresses from a mild to a severe form of infection, the exosome's microRNA (miRNA) composition might change, which may contribute to pathogenesis. In this study, a comprehensive analysis of serum exosomal miRNAs was performed and their involvement in dengue virus‐induced disease progression in an Indian cohort was assessed. Small RNA‐seq showed 50 differentially expressed exosomal miRNAs that were significantly dysregulated during dengue infection. After extensive validation, miR‐96‐5p was found to be significantly upregulated, whereas miR‐146a‐5p was significantly downregulated with the progression of disease to severe form. Interestingly, a strong positive correlation was found between the expression levels of miR‐96‐5p and miR‐146a‐5p and the platelet levels of the patients. Further, study of miR‐146a‐5p showed that it regulates the expression of the proteins which are involved in the immune responses. These results suggest that miR‐96‐5p and miR‐146a‐5p could be used as diagnostic and prognostic markers for dengue disease progression, in addition to the already available biochemical and pathological parameters.
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Dengue virus is an arbovirus belonging to class Flaviviridae Its clinical manifestation ranges from asymptomatic to extreme conditions (dengue hemorrhagic fever/dengue shock syndrome). A lot of research has been done on this ailme...
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Dengue virus is an arbovirus belonging to class Flaviviridae Its clinical manifestation ranges from asymptomatic to extreme conditions (dengue hemorrhagic fever/dengue shock syndrome). A lot of research has been done on this ailment, yet there is no effective treatment available for the disease. This review provides the systematic understanding of all dengue proteins, role of its structural proteins (C-protein, E-protein, prM) in virus entry, assembly, and secretion in host cell, and nonstructural proteins (NS1, NS2a, NS2b, NS3, NS4a, NS4b, and NS5) in viral assembly, replication, and immune evasion during dengue progression and pathogenesis. Furthermore, the review has highlighted the controversies related to the only commercially available dengue vaccine, that is, Dengvaxia, and the risk associated with it. Lastly, it provides an insight regarding various approaches for developing an effective anti-dengue treatment.
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Background Clinical symptoms of Dengue vary from mild febrile illness to severe infection. A potent pro-inflammatory cytokine, IL-17, secreted by mainly Th17 cells mediate inflammation and autoimmune dis...
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Background Clinical symptoms of Dengue vary from mild febrile illness to severe infection. A potent pro-inflammatory cytokine, IL-17, secreted by mainly Th17 cells mediate inflammation and autoimmune diseases. Role of IL-17 in pathogenesis of dengue virus (DV) infection is not clear.
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In recent efficacy trials of a dengue vaccine candidate, about 7-15% of volunteers in the control group manifested at least one of the three dengue hemorrhagic fever (DHF)-defining abnormalities (hemorrhage, thrombocytopenia, and ...
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In recent efficacy trials of a dengue vaccine candidate, about 7-15% of volunteers in the control group manifested at least one of the three dengue hemorrhagic fever (DHF)-defining abnormalities (hemorrhage, thrombocytopenia, and plasma leakage) during symptomatic dengue virus infection. A high risk of developing DHF observed in secondarily infected persons is related to an increased viral burden. Complex interactions between structurally heterogeneous viral particles and pre-existing antibodies specific for the viral envelope glycoproteins, E and prM, are thought to play a role in enhancing virus replication. Concomitant high level of circulating NS1, a virally encoded glycoprotein that is essential for viral RNA replication, may cause plasma leakage through its direct and indirect effects on the vascular endothelial cells. Cross-reaction of anti-NS1 antibodies generated during dengue virus infection with platelets may lead to thrombocytopenia. Dengue serotype cross-reactive T cells rapidly expand during the secondary infection, and their levels in the circulation are associated with the development of DHF. However, the role of T cells in mediating an increase in vascular permeability at the tissue level remains unclear.
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Dengue is currently the most important viral disease transmitted to man by arthropods, whe- ther measured by the number of cases or number of deaths. Prevalence of the disease is highest in tropical Asia, intermediate in tropical ...
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Dengue is currently the most important viral disease transmitted to man by arthropods, whe- ther measured by the number of cases or number of deaths. Prevalence of the disease is highest in tropical Asia, intermediate in tropical America, and lowest in Tropical Africa. Four distinct dengue viruses have been Identified. Types 2 and 3 appear to be more pathoge- Nic on the average than types 1 and 4, but all four can Cause severe or fatal dengue syndromes.
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Dengue is a very rapidly growing public health problem being currently faced by ∼40% of the global population living in more than a hundred tropical and sub-tropical countries. It is a viral disease, caused by four types of dengu...
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Dengue is a very rapidly growing public health problem being currently faced by ∼40% of the global population living in more than a hundred tropical and sub-tropical countries. It is a viral disease, caused by four types of dengue viruses, transmitted by mosquitoes, to an estimated 50 million people each year. Vector control methods to contain transmission have not been successful and there is currently no useful diagnostic test, drug or vaccine to combat dengue disease. However, as a result of the heightened awareness of its magnitude and its potential to spread beyond the tropical world, dengue has begun to emerge out of the list of neglected diseases in recent years. New interest in this disease has drawn scientists from multiple disciplines into the dengue arena. This has resulted in novel insights into several aspects of dengue virus biology and identified potential drug targets. Several tetravalent vaccines are being developed. Newer animal models that mirror some of the salient features of dengue disease are becoming available to investigate the mechanism of pathogenesis and to aid in drug and vaccine discovery efforts. The realization that therapeutic and prophylactic intervention can be cost-effective has resulted in vigorous industry-driven translational initiatives to develop drugs and vaccines. Dengue research is at a critical juncture and the implementation of existing knowledge supplemented by a better understanding of pathogenesis promises to make a tangible impact in the combat against dengue in the coming years.
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Dengue virus infection is a self-limited condition, which is of particular importance in tropical and subtropical regions and for which no specific treatment or effective vaccine is available. There are several hypotheses explaini...
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Dengue virus infection is a self-limited condition, which is of particular importance in tropical and subtropical regions and for which no specific treatment or effective vaccine is available. There are several hypotheses explaining dengue pathogenesis. These usually refer to host immune responses, including antibody-dependent enhancement, cytokine expression, and dengue virus particles including NS1 protein, which lead to cell death by both apoptosis and pyroptosis. A clear understanding of the pathogenesis should facilitate the development of vaccines and therapies. This review focuses on the immunopathogenesis in relation to clinical manifestations and patterns of cell death, focusing on the pathogenesis of severe dengue.
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Dengue viruses (DENVs) exploit monocytes and macrophages for tropism and replication, therefore, establishing a long-term reservoir. However, their roles in dengue pathogenesis remains unclear. Here, using the human monocytic cell...
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Dengue viruses (DENVs) exploit monocytes and macrophages for tropism and replication, therefore, establishing a long-term reservoir. However, their roles in dengue pathogenesis remains unclear. Here, using the human monocytic cell line THP-1, human primary monocytes, and non-human primate models, we show that DENV-infected monocytes represent suitable carriers for circulatory viral dissemination. Monocyte-derived macrophages expressing M2 surface markers at the gene level efficiently replicated, while the productivity of monocyte replication was low. However, attachment of DENVs to the cellular surface of monocytes was similar to that of macrophages. Furthermore, after differentiation with type-2 cytokines, DENV-attached monocytes could replicate DENVs. Productive DENV infection was confirmed by intravenous injection of DENVs into nonhuman primate model, in which, DENV attachment to monocytes was positively correlated with viremia. These results provide insight into the role of circulating monocytes in DENV infection, suggesting that monocytes directly assist in DENV dissemination and replication during viremia and could be applied to design antiviral intervention.
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