Ribosome profiling analysis of Dengue Virus
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE69602 | GEO | 2016/09/01
SECONDARY ACCESSION(S): PRJNA285961
REPOSITORIES: GEO
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Project description:Dengue virus is an + strand RNA virus. We have carried our infections of human cells with Dengue and analyzed the translation, replication, and localization of the Dengue RNA. This allowed for clear definition of the life cycle of the Dengue virus inside a host cell. We also assessed the host response to Dengue virus, finding that a large fraction of the translational response is due to Interferon function. Translational and transcriptional analysis of the cellular response to Dengue virus infection
2016-09-01 | E-GEOD-69602 | biostudies-arrayexpress
Project description:Dengue is a pan-tropic public health problem. In children, dengue shock syndrome (DSS) is the most common life-threatening complication. Predicting patients who may develop DSS may improve triage and treatment. To this end, we conducted a nested case-control comparison of the early host-transcriptional features in 24 DSS patients and 56 sex-, age-, virus serotype-matched uncomplicated dengue patients. In the first instance we defined the âearly dengueâ profile. The transcriptional signature in acute versus convalescent samples (â¤72hrs post illness-onset) was defined by an over-abundance of interferon-inducible transcripts (31% of the 551 over-abundant transcripts), and canonical gene ontology terms that included response to virus, immune response, innate immune response and inflammatory response. Pathway and network analysis identified STAT1, STAT2, STAT3, IRF7, IRF9, IRF1, CEBPB and SP1 as key transcriptional factors mediating the early response. Strikingly, the only differences in the transcriptional signatures of early DSS and uncomplicated dengue cases was the greater abundance of several neutrophil-associated transcripts in patients who progressed to DSS, a finding supported by higher plasma concentrations of several canonical proteins associated with neutrophil-degranulation (BPI, ELA2, DEF1A). Elevated levels of neutrophil-associated transcripts were independent of the neutrophil count and also the genotype of the infecting virus, as genome-length sequences of DENV-1 (n=15) and DENV-2 (n=3) viruses sampled from DSS patients were phylogenetically indistinguishable from those sampled from uncomplicated dengue patients (32 DENV-1 and 9 DENV-2). Collectively, these data suggest an hitherto unrecognised association between neutrophil activation, pathogenesis and the development of DSS and point to future strategies for guiding prognosis. 112 patients: 80 with uncomplicated dengue, 32 with dengue shock syndrome
2010-10-29 | E-GEOD-25001 | biostudies-arrayexpress
Project description:DNA microarrays and specific RT-PCR assays were used to reveal transcriptional patterns in the blood of children presenting with dengue shock syndrome (DSS) and well-matched patients with uncomplicated dengue. The transcriptome of patients with acute uncomplicated dengue was characterized by a metabolically demanding "host defense" profile; transcripts related to oxidative metabolism, interferon signaling, protein ubiquination, apoptosis and cytokines were prominent. In contrast, the transcriptome of DSS patients was surprisingly benign, particularly with regard to transcripts derived from apoptotic and type I interferon pathways. These data highlight significant heterogeneity in the type or timing of host transcriptional immune responses precipitated by DENV infection independent of the duration of illness. In particular, they suggest that if transcriptional events in the blood compartment contribute to capillary leakage leading to hypovolemic shock, they occur before cardiovascular decompensation occurs, a finding that has implications for rational adjuvant therapy in this syndrome. Whole blood transcriptional profiles of children infected with dengue virus with different clinical outcomes were compared. The subjects including 9 acute dengue shock samples, 9 acute uncomplicated dengue samples, 6 autologous follow up dengue samples and 6 autologous follow up uncomplicated dengue patients. Microarray data was normalised using Genespring GX7 software, statistical analysis was performed in Multiexperiment viewer software. Pathway analysis was performed using Ingenuity Pathway analysis online software.
2008-12-18 | E-GEOD-13052 | biostudies-arrayexpress
Project description:Dengue is a pan-tropic public health problem. In children, dengue shock syndrome (DSS) is the most common life-threatening complication. Predicting patients who may develop DSS may improve triage and treatment. To this end, we conducted a nested case-control comparison of the early host-transcriptional features in 24 DSS patients and 56 sex-, age-, virus serotype-matched uncomplicated dengue patients. In the first instance we defined the “early dengue” profile. The transcriptional signature in acute versus convalescent samples (≤72hrs post illness-onset) was defined by an over-abundance of interferon-inducible transcripts (31% of the 551 over-abundant transcripts), and canonical gene ontology terms that included response to virus, immune response, innate immune response and inflammatory response. Pathway and network analysis identified STAT1, STAT2, STAT3, IRF7, IRF9, IRF1, CEBPB and SP1 as key transcriptional factors mediating the early response. Strikingly, the only differences in the transcriptional signatures of early DSS and uncomplicated dengue cases was the greater abundance of several neutrophil-associated transcripts in patients who progressed to DSS, a finding supported by higher plasma concentrations of several canonical proteins associated with neutrophil-degranulation (BPI, ELA2, DEF1A). Elevated levels of neutrophil-associated transcripts were independent of the neutrophil count and also the genotype of the infecting virus, as genome-length sequences of DENV-1 (n=15) and DENV-2 (n=3) viruses sampled from DSS patients were phylogenetically indistinguishable from those sampled from uncomplicated dengue patients (32 DENV-1 and 9 DENV-2). Collectively, these data suggest an hitherto unrecognised association between neutrophil activation, pathogenesis and the development of DSS and point to future strategies for guiding prognosis.
2010-10-29 | GSE25001 | GEO
Project description:The ability of many viruses to manipulate the host antiviral immune response often results in complex host-pathogen interactions. In order to study the interaction of dengue virus (DENV) with the Aedes aegypti immune response, we have characterized the DENV infection-responsive transcriptome of the immune-competent A. aegypti cell line Aag2. As in mosquitoes, DENV infection transcriptionally activated the cell line Toll pathway and a variety of cellular physiological systems. Most notably, however, DENV infection down-regulated the expression levels of numerous immune signaling molecules and antimicrobial peptides (AMPs). Functional assays showed that transcriptional induction of AMPs from the Toll and IMD pathways in response to bacterial challenge is impaired in DENV-infected cells. In addition, Escherichia coli, a gram-negative bacteria species, grew better when co-cultured with DENV-infected cells than with uninfected cells, suggesting a decreased production of AMPs from the IMD pathway in virus-infected cells. Pre-stimulation of the cell line with gram-positive bacteria prior to DENV infection had no effect on DENV titers, while pre-stimulation with gram-negative bacteria resulted in an increase in DENV titers. These results indicate that DENV is capable of actively suppressing immune responses in the cells it infects, a phenomenon that may have important consequences for virus transmission and insect physiology. Infected (dengue virus or heat-inactivated dengue virus) vs. naive cells. 3 replicates each.
2011-10-31 | E-GEOD-33274 | 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: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:Unbiased forward genetic screen to identify host factors for a Dengue virus mutant
2023-06-30 | E-MTAB-11119 | biostudies-arrayexpress
Project description:Microarray data was used to study the gene expression changes following dengue infection at various time points to identify host genes and pathways responsible for dengue virus replication Keywords: time course
2006-11-16 | GSE6048 | 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