Genome-Wide Expression Profiling Deciphers Host Responses Altered during Dengue Shock Syndrome and Reveals the Role of Innate Immunity in Severe Dengue.
Summary of "Genome-Wide Expression Profiling Deciphers Host Responses Altered during Dengue Shock Syndrome and Reveals the Role of Innate Immunity in Severe Dengue."
Deciphering host responses contributing to dengue shock syndrome (DSS), the life-threatening form of acute viral dengue infections, is required to improve both the differential prognosis and the treatments provided to DSS patients, a challenge for clinicians. METHODOLOGY/PRINCIPAL
Based on a prospective study, we analyzed the genome-wide expression profiles of whole blood cells from 48 matched Cambodian children: 19 progressed to DSS while 16 and 13 presented respectively classical dengue fever (DF) or dengue hemorrhagic fever grades I/II (DHF). Using multi-way analysis of variance (ANOVA) and adjustment of p-values to control the False Discovery Rate (FDR<10%), we identified a signature of 2959 genes differentiating DSS patients from both DF and DHF, and showed a strong association of this DSS-gene signature with the dengue disease phenotype. Using a combined approach to analyse the molecular patterns associated with the DSS-gene signature, we provide an integrative overview of the transcriptional responses altered in DSS children. In particular, we show that the transcriptome of DSS children blood cells is characterized by a decreased abundance of transcripts related to T and NK lymphocyte responses and by an increased abundance of anti-inflammatory and repair/remodeling transcripts. We also show that unexpected pro-inflammatory gene patterns at the interface between innate immunity, inflammation and host lipid metabolism, known to play pathogenic roles in acute and chronic inflammatory diseases associated with systemic vascular dysfunction, are transcriptionnally active in the blood cells of DSS children. CONCLUSIONS/
We provide a global while non exhaustive overview of the molecular mechanisms altered in of DSS children and suggest how they may interact to lead to final vascular homeostasis breakdown. We suggest that some mechanisms identified should be considered putative therapeutic targets or biomarkers of progression to DSS.
French Army Biomedical Research Institute (Institut de recherche biomédicale des armées, IRBA), Antenne de Marseille-IMTSSA; Unité de Virologie, Marseille, France.
This article was published in the following journal.
Name: PloS one
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20652028
- DOI: http://dx.doi.org/10.1371/journal.pone.0011671
Medical and Biotech [MESH] Definitions
Gene Expression Profiling
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
The diagnosis and treatment of human responses of individuals and groups to actual or potential health problems with the characteristics of altered functional ability and altered life-style. (American Nurses Association & Association of Rehabilitation Nurses. Standards of Rehabilitation Nursing Practice, 1986, p.2)
Animals, Genetically Modified
ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.
Plants, Genetically Modified
PLANTS, or their progeny, whose GENOME has been altered by GENETIC ENGINEERING.
Host Vs Graft Reaction
The immune responses of a host to a graft. A specific response is GRAFT REJECTION.
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