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

Long Truong Hoang, Martin L. Hibberd, Hien Tinh Tran, Minh Dung Nguyen, Van Ngoc Tran, Jeremy Farrar, Bridget Wills, Cameron P. Simmons

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49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)537-546
Number of pages10
JournalJournal of Infectious Diseases
Volume199
Issue number4
DOIs
Publication statusPublished - 15 Feb 2009
Externally publishedYes

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