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Identification and control of host innate disease causing responses to dengue infection

ABSTRACT: Our hypothesis is that dengue induces different innate immune responses in patients with mild respective severe dengue. We further hypothesize that severe dengue infection is a consequence of an over reactive inflammatory response which could be inhibited in an early stage by immune suppressants. We hypothesize that the drugs used in this study induce a down regulated inflammatory response; VP-16 by triggering apoptosis and Rosiglitazone by inhibiting NFkB related cytokine production In-vitro dengue infected U937, transcriptional assessment

ORGANISM(S): Homo sapiens

SUBMITTER: Ahmad Nazri Mohamed Naim

PROVIDER: E-GEOD-28985 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Identification and control of host innate disease causing responses to dengue infection

Project description:Our hypothesis is that dengue induces different innate immune responses in patients with mild respective severe dengue. We further hypothesize that severe dengue infection is a consequence of an over reactive inflammatory response which could be inhibited in an early stage by immune suppressants. We hypothesize that the drugs used in this study induce a down regulated inflammatory response; VP-16 by triggering apoptosis and Rosiglitazone by inhibiting NFkB related cytokine production

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2014-04-01 | E-GEOD-28991 | biostudies-arrayexpress

Influenzavirus serotype association to global whole blood transcriptional changes

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Immune correlates of early prednisolone therapy in children and adolescents with dengue

Project description:Dengue is the most important arboviral infection of humans. A host pro-inflammatory immune response is widely believed to contribute to the clinical complications that occur in some patients with dengue. Here, immune correlates of early prednisolone therapy were defined in Vietnamese dengue patients enrolled in a randomized controlled trial, comparing a three day regimen of high (2mg/kg) or low (0.5mg/kg) dose prednisolone with placebo. Prednisolone conferred a small change in the whole blood gene expression profile, with 81 transcripts from 64 genes differentially abundant between high-dose prednisolone and placebo treated patients. A prominent theme in the prednisolone gene expression signature was the under-abundance of transcripts from genes associated with T and NK cell cytolytic effector functions. Surprisingly, prednisolone therapy was not associated with attenuation of early-convalescent T cell responses or plasma cytokine levels. Collectively, these findings are consistent with a remarkably benign influence of prednisolone on immune response parameters in dengue patients, and are in line with the trial evidence showing lack of impact on clinical laboratory endpoints and clinical phenotype. The gene expression microarray assay was conducted on samples from the first 123 consecutive patients (placebo, 40; 0.5mg/kg prednisolone, 42; 2.0mg/kg prednisolone, 41).

2012-12-31 | E-GEOD-40165 | biostudies-arrayexpress

Genome-wide gene expression analysis of human whole-blood samples in in response to dengue disease

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2011-12-31 | E-GEOD-28405 | biostudies-arrayexpress

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Project description:Background: dengue is a potentially life-threatening viral infection. Early prognostic markers of severe complications may improve case management and reduce dengue-related mortalities. This study aimed to identify circulating microRNAs (miRNAs) as biomarkers for predicting severe dengue. Methods: Serum samples from dengue-infected patients were collected on the first day of admission. Patients were followed up for 14 days after admission to determine the final diagnosis. Participants were divided into non-severe and severe dengue, as defined by WHO 2009 criteria. Circulating microtranscriptome analysis was performed using the NanoString miRNA Expression Assay. The expression level of candidate miRNAs were then validated by quantitative reverse transcription-PCR (qRT-PCR) method. Findings: The discovery cohort (N=19) lead to the identification of 37 differentially expressed miRNAs between the two groups. Six miRNAs (miR122-5p, miR1246, miR1303, miR574-5p, miR30d-5p, and miR424-5p) were selected and further validated in the larger cohort (N=135). The qRT-PCR analysis confirmed that the six miRNAs expression levels were significantly higher in the severe dengue group compared to the non-severe group. Based on receiver operating characteristic (ROC) analysis, miR574-5p and miR1246 displayed the highest diagnostic performance in discriminating between severe from non-severe dengue (AROC curve =0·83). Additionally, miR574-5p and miR1246 had high sensitivity and high negative predictive value for detecting severe dengue. Multivariate analysis suggested that serum miR574-5p was an independent predictor of severe dengue (odds ratio 3·30, 95% CI 1·81-6·04; p<0·001). Interpretation: Circulating miRNAs, especially miR-574-5p and miR-1246, could be promising diagnostic and prognostic biomarkers for severe dengue.

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2021-09-21 | GSE174482 | GEO

In vivo molecular signatures of severe dengue infection revealed by viscRNA-Seq

Project description:Dengue virus infection can result in severe symptoms including shock and hemorrhage, but an understanding of the molecular correlates of disease severity is lacking. Bulk transcriptomics on blood samples are difficult to interpret because the blood is composed of different cell types that may react differently to virus infection. Dengue virus RNA can be detected in human plasma, however identifying the cells carrying dengue virus through the bloodstream in vivo has proven challenging. Here we used our recently developed viscRNA-Seq approach to profile transcriptomes of thousands of single blood peripheral mononuclear cells from 6 human subjects with dengue fever and severe dengue, as well as to characterize the cell types associated with dengue virus in the human blood. We found that although no bulk transcriptome marker for severe dengue exists, the expression of MX2 in naive B cells, of CD163 in CD14+/CD16+ monocytes and of other genes in specific cell types is highly predictive for severe dengue. We detected virus-associated cells in the blood of two severe dengue patients with high viral load and discovered the majority of these to be B cells expressing germline IgM or IgD immunoglobulin chains and naive markers but also showing signs of activation and expression of CD69, CXCR4, and other surface receptors. In bystander B cells we detected signs of strong immune activation, parallel hypersomatic evolution and, in one severe degue subject, an anomalously large clone of highly mutated, IgG1 plasmablasts that could be reactive to dengue virus. This study presents a high-resolution molecular exploration into dengue virus infection in humans and can be generalized to any RNA virus.

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