Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA103087 | ENA |
REPOSITORIES: ENA
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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: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: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:The goal of this study was to compare the transcriptional profile (RNA-seq) of Dengue virus 2 and mock infected cells at 24 and 36 hours post infection. Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication. A549 cells where infected with Dengue virus 2 or mock and after 24 and 36 hours post infection mRNA was purified. Then the transcriptional profile of these cells was analyzed using RNA-seq.
2016-08-09 | E-GEOD-84285 | 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:West Nile virus (WNV) is an emerging mosquito-borne flavivirus, related to dengue virus and Zika virus. To gain insight into host pathways involved in WNV infection, we performed a systematic affinity-tag purification mass spectrometry (AP-MS) study to identify 259 WNV-interacting human proteins. RNAi screening revealed 26 genes that both interact with WNV proteins and influence WNV infection. We found that WNV, dengue and Zika virus capsids interact with a conserved subset of proteins that impact infection. These include the exon-junction complex (EJC) recycling factor, PYM1, which is antiviral against all three viruses. The EJC has roles in nonsense-mediated decay (NMD), and we found that both the EJC and NMD are antiviral. Mechanistically, we found that the EJC protein RBM8A directly binds WNV RNA. To counteract this antiviral defense, flavivirus infection inhibits NMD and the interaction of capsid with PYM1 interferes with EJC protein function and localization. Moreover, depletion of PYM1 attenuates RBM8A binding to viral RNA, suggesting that WNV sequesters PYM1 to protect viral RNA from decay. Together, these data suggest a complex interplay between the virus and host in regulating NMD and the EJC complex.
2019-11-14 | PXD011728 | Pride
Project description:RNA interference (RNAi) functions as the major host antiviral defense in insects, while less is understood about how to utilize antiviral RNAi in controlling viral infection in insects. Enoxacin belongs to the family of synthetic antibacterial compounds based on a fluoroquinolone skeleton that has been previously found to enhance RNAi in mammalian cells. In this study, we showed that enoxacin efficiently inhibited viral replication of Drosophila C virus (DCV) and Cricket paralysis virus (CrPV) in cultured Drosophila cells. Enoxacin promoted the loading of Dicer-2-processed virus-derived siRNA into the RNA-induced silencing complex, thereby enhancing antiviral RNAi response in infected cells. Moreover, enoxacin treatment elicited an RNAi-dependent in vivo protective efficacy against DCV or CrPV challenge in adult fruit flies. In addition, enoxacin also inhibited replication of flaviviruses, including Dengue virus and Zika virus, in Aedes mosquito cells in an RNAi-dependent manner. Together, our findings demonstrated that enoxacin can enhance RNAi in insects, and enhancing RNAi by enoxacin is an effective antiviral strategy against diverse viruses in insects, which may be exploited as a broad-spectrum antiviral agent to control vector transmission of arboviruses or viral diseases in insect farming.
2021-11-22 | GSE189204 | 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
Project description:Flaviviruses, including Dengue and Zika, are widespread human pathogens; however, no broadly active therapeutics exist to fight infection. Recently, remodeling of endoplasmic reticulum (ER) proteostasis by pharmacologic regulators, such as compound 147, was shown to correct pathologic ER imbalances associated with protein misfolding diseases. Here, we establish a new activity of compound 147 as an effective host-centered antiviral agent against flaviviruses. Compound 147 reduces infection by attenuating the infectivity of secreted virions without causing toxicity in host cells. 147 is a preferential activator of the ATF6 pathway of the ER unfolded protein response, which requires targeting of cysteine residues primarily on protein disulfide isomerases (PDIs). We find that the antiviral activity of 147 is independent of ATF6 induction but does require modification of reactive thiols on protein targets. Targeting PDIs and additional non-PDI targets using RNAi and other small molecule inhibitors was unable to recapitulate the antiviral effects, suggesting a unique polypharmacology may mediate the activity. Importantly, 147 can impair infection of multiple strains of Dengue and Zika virus, indicating that it is suitable as a broad-spectrum antiviral agent.
2021-01-18 | PXD022453 | Pride
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