Vitamin D Enhances Antiviral Responses in Dengue Virus-Infected Macrophages by Modulating Early-Response Gene Expression
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PROVIDER: PRJNA1263729 | ENA |
REPOSITORIES: ENA
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Project description:Dengue virus (DENV), the etiological agent of dengue fever, remains a global health concern, leading to severe illness and death in the absence of any definitive cure. Research has shown that vitamin D may reduce DENV replication in vitro and that dengue patients with low or deficient vitamin D levels are at higher risk of severe dengue. Studies indicate that viral replication is inhibited in human monocyte-derived macrophages (MDM) differentiated in the presence of vitamin D (D3MDM), suggesting that vitamin D may prevent DENV entry into host cells. However, despite these findings, the role of vitamin D in regulating the temporal expression patterns of genes as early, mid, and late transcriptional profile of DENV-infected macrophages remains unclear. Therefore, utilizing a kinetic transcriptomic profile is crucial. This approach provides detailed insights into the dynamic changes in gene expression over time, helping to clarify how vitamin D can modulate the immune response at critical stages of DENV infection. To address the transcriptional dynamics, we conducted a comprehensive analysis of gene expression patterns in MDM and D3MDM infected with Dengue virus serotype 2 (DENV-2). Utilizing bulk RNA sequencing alongside a standard viral growth curve, we systematically analyzed transcriptional kinetics by selecting key time points: 1.5, 3, 5.5, and 10 hours post-infection (h.p.i.) to monitor early viral entry and replication events and 24 h.p.i. to assess gene expression during peak viral particle production. Our temporal analysis revealed a progressive increase in cellular transcripts within the first hour of infection, with a more pronounced gene expression pattern in DENV-2-infected MDM compared to DENV-2-infected D3MDM at this early stage. Enrichment analysis indicated a reduced inflammatory response in DENV-2-infected D3MDM. Additionally, transcription factor analysis suggested diminished NF-κB signaling, but enhanced IRF5 activity was elevated in the DENV-2-infected D3MDM. High-dimensional clustering analysis identified nine unique gene clusters across both macrophage types, with notable upregulation of genes associated with antiviral activity, including IDO1, ISG20, OASL, IFI44L, RSAD2, IFIT1, MX1, EPSTI1, CXCL10, and CXCL11 in DENV-2-infected D3MDM at 1.5 h.p.i., suggesting an enhanced early antiviral response. These findings indicate that vitamin D modulates the magnitude and diversity of the early transcriptional responses, highlighting its potential as a therapeutic option to mitigate DENV severity.
2025-08-27 | GSE297386 | GEO
Project description:Analysis of the host response to dengue virus at gene expression level. The hypothesis tested in the present study was that dengue virus triggers and regulate different pathaway with different kinetics controlling the antiviral, the inflammatory and the apoptotic response in primary human DC. Results provide important information of the response to DC to dengue virus showing that antioxidant genes are early stimulated after denv infection reflecting an early production of reactive oxygen species. Interestingely, we demonstrated that ROS production and antiviral and apoptotic responses intersect since chemical inhibition of ROS impairs antiviral and apoptotic responses in these cells. Total RNA obtained from in vitro dengue infected primary human dendritic cells at 0, 6, 12, 18, 24 hours compared to uninfected cells at time 0
2014-12-18 | E-GEOD-58278 | biostudies-arrayexpress
Project description:Analysis of the host response to dengue virus at gene expression level. The hypothesis tested in the present study was that dengue virus triggers and regulate different pathaway with different kinetics controlling the antiviral, the inflammatory and the apoptotic response in primary human DC. Results provide important information of the response to DC to dengue virus showing that antioxidant genes are early stimulated after denv infection reflecting an early production of reactive oxygen species. Interestingely, we demonstrated that ROS production and antiviral and apoptotic responses intersect since chemical inhibition of ROS impairs antiviral and apoptotic responses in these cells.
2014-12-18 | GSE58278 | GEO
Project description:Sepsis remains a significant challenge in critical care, with early inflammation and infection control being key therapeutic hurdles. Recent studies have highlighted the potential role of vitamin B12 in modulating immune responses and its therapeutic applications in sepsis. This study investigates the impact of vitamin B12 and its transport protein, transcobalamin II (TCN2), on macrophage polarization and inflammatory responses in sepsis. We found that vitamin B12 levels are significantly reduced in sepsis patients and correlate negatively with pro-inflammatory cytokines such as IL-6, TNFα, and CRP. In mouse models, vitamin B12 supplementation improved survival rates, reduced lung injury, and modulated macrophage polarization towards an anti-inflammatory M2 phenotype. Mechanistically, vitamin B12 interacts with PTGS2, promoting its degradation and inhibiting PGE2 production. TCN2, the key transporter of vitamin B12, regulates TLR4 activation and macrophage M1 polarization. TCN2 knockout mice exhibited reduced inflammation and improved survival in LPS-induced sepsis, but increased bacterial load in CLP models. Additionally, TCN2 enhances glucose uptake and glycolysis through interaction with GLUT1, promoting M1 macrophage polarization. These findings suggest that vitamin B12 and TCN2 play crucial roles in modulating the inflammatory response and could be potential therapeutic targets in sepsis.
2025-12-31 | GSE283884 | GEO
Project description:Dengue fever is an important tropical illness for which there is currently no virus-specific treatment. To shed light on mechanisms involved in the cellular response to dengue virus (DV), we assessed gene expression changes, using Affymetrix GeneChips (HG-U133A), of infected primary human cells and identified changes common to all cells. The common response genes included a set of 23 genes significantly induced upon DV infection of human umbilical vein endothelial cells (HUVECs), dendritic cells (DCs), monocytes, and B cells (analysis of variance, P < 0.05). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), one of the common response genes, was identified as a key link between type I and type II interferon response genes. We found that DV induces TRAIL expression in immune cells and HUVECs at the mRNA and protein levels. The induction of TRAIL expression by DV was found to be dependent on an intact type I interferon signaling pathway. A significant increase in DV RNA accumulation was observed in anti-TRAIL antibody-treated monocytes, B cells, and HUVECs, and, conversely, a decrease in DV RNA was seen in recombinant TRAIL-treated monocytes. Furthermore, recombinant TRAIL inhibited DV titers in DV-infected DCs by an apoptosis-independent mechanism. These data suggest that TRAIL plays an important role in the antiviral response to DV infection and is a candidate for antiviral interventions against DV. We used Affymetrix microarrays to study the response of human host cells to dengue virus (DV). Keywords: virus infection of multiple cell types
2008-01-05 | GSE9378 | GEO
Project description: Not available
| S-EPMC12370076 | biostudies-literature
Project description:Dengue fever is an important tropical illness for which there is currently no virus-specific treatment. To shed light on mechanisms involved in the cellular response to dengue virus (DV), we assessed gene expression changes, using Affymetrix GeneChips (HG-U133A), of infected primary human cells and identified changes common to all cells. The common response genes included a set of 23 genes significantly induced upon DV infection of human umbilical vein endothelial cells (HUVECs), dendritic cells (DCs), monocytes, and B cells (analysis of variance, P < 0.05). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), one of the common response genes, was identified as a key link between type I and type II interferon response genes. We found that DV induces TRAIL expression in immune cells and HUVECs at the mRNA and protein levels. The induction of TRAIL expression by DV was found to be dependent on an intact type I interferon signaling pathway. A significant increase in DV RNA accumulation was observed in anti-TRAIL antibody-treated monocytes, B cells, and HUVECs, and, conversely, a decrease in DV RNA was seen in recombinant TRAIL-treated monocytes. Furthermore, recombinant TRAIL inhibited DV titers in DV-infected DCs by an apoptosis-independent mechanism. These data suggest that TRAIL plays an important role in the antiviral response to DV infection and is a candidate for antiviral interventions against DV. We used Affymetrix microarrays to study the response of human host cells to dengue virus (DV). Experiment Overall Design: For three human cell types, RNA was extracted and hybridized on Affymetrix microarrays. We compared a total of 10 samples. Five were infected in vitro for 48 hours with DV, including HUVECs (n=2), monocytes (n=2), and B-cells (n=1). Five were mock-infected controls of the same cell types and numbers. From these samples, were identified 23 genes that were induced by DV infection in all of the cell types.
2008-06-16 | E-GEOD-9378 | biostudies-arrayexpress
Project description:TBK1 plays a pivotal role in innate antiviral immunity, serving as a critical mediator downstream of various pattern recognition receptors (PRRs). TBK1 activity is tightly regulated by post-translational modifications (PTMs) including ubiquitination to maintain innate immune homeostasis. Here, we identify the Deltex E3 ubiquitin ligase 2 (DTX2) as a positive regulator of innate antiviral signaling in response to RNA viruses. We find that DTX2 overexpression enhances antiviral signaling, whereas loss of DTX2 evidently reduces antiviral responses. Mechanistically, we demonstrated that DTX2 directly interacts with TBK1 and promotes TBK1 K63-linked polyubiquitination to regulate antiviral signaling. Collectively, our study reveals that DTX2 plays a novel positive regulatory role in antiviral signaling by modulating the K63-linked ubiquitination of TBK1 to maintain the balance of innate antiviral immune responses.
2025-01-04 | GSE285743 | GEO
Project description:Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). While the mechanisms that lead to vascular permeability are unknown, the endothelium plays a central role in regulating fluid and cellular efflux from capillaries. Thus, dysregulation of endothelial cells functions by dengue virus infection may contribute to pathogenesis and severe disease. We used microarrays to investigate the effect of dengue virus infection on gene expression within primary human endothelial cells at various times post infection and identified numerous upregulated antiviral and immune response genes.
2012-04-11 | GSE34628 | GEO
Project description:Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). While the mechanisms that lead to vascular permeability are unknown, the endothelium plays a central role in regulating fluid and cellular efflux from capillaries. Thus, dysregulation of endothelial cells functions by dengue virus infection may contribute to pathogenesis and severe disease. We used microarrays to investigate the effect of dengue virus infection on gene expression within primary human endothelial cells at various times post infection and identified numerous upregulated antiviral and immune response genes. Early passage primary endothelial cells (HUVECs) were mock infected (no virus) or infected with dengue virus and total RNA collected at 3 timepoints: 12, 24, and 48 hours post infection. Multiple timepoints were analyzed to identify changes in gene expression levels over time. Gene expression from both mock infected and dengue virus infected endothelial cells was evaluated to determine fold induction at each timepoint.
2012-04-10 | E-GEOD-34628 | biostudies-arrayexpress