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.
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.
Long
Hoang Truong
HT
Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Hibberd
Martin L
ML
Genome Institute of Singapore, Singapore.
Hien
Tran Tinh
TT
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Dung
Nguyen Minh
NM
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Van Ngoc
Tran
T
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Farrar
Jeremy
J
Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
Wills
Bridget
B
Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
Simmons
Cameron P
CP
Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
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
D012333:RNA, Messenger