title: Patterns of gene transcript abundance in the blood of children with severe or uncomplicated dengue highlight differences in disease evolution and host response to dengue virus infection.
abstract: DNA microarrays and specific reverse-transcription polymerase chain reaction 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 patients with DSS 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 dengue virus 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, a finding that has implications for rational adjuvant therapy in this syndrome.
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Hoang Truong
authors.initials: HT
authors.lastname: Long
authors.affiliation: Genome Institute of Singapore, Singapore.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Minh
authors.initials: NM
authors.lastname: Dung
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Tran
authors.initials: T
authors.lastname: Van Ngoc
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Bridget
authors.initials: B
authors.lastname: Wills
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D002648:Child; D003715:Dengue / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000472:pathogenicity; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019595:Severe Dengue / Q000235:genetics / Q000276:immunology*; D018709:Statistics, Nonparametric
chemical_list: D012333:RNA, Messenger