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.

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.
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DOI:
10.1086/596507
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发表时间:
2009-02-15
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Simmons CP
Simmons CP
中科院分区:
其他
文献类型:
--
作者:
Long HT;Hibberd ML;Hien TT;Dung NM;Van Ngoc T;Farrar J;Wills B;Simmons CP

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DNA微阵列和特异性逆转录聚合酶链反应检测被用来揭示登革热休克综合征(DSS)儿童和匹配良好的无并发症登革热患者血液中的转录模式。急性无并发症登革热患者的转录组的特点是代谢要求的“宿主防御”配置文件;与氧化代谢,干扰素信号,蛋白质泛素化,细胞凋亡和细胞因子相关的转录是突出的。相比之下,DSS患者的转录组是令人惊讶的良性,特别是关于来自凋亡和I型干扰素途径的转录物。这些数据突出了登革病毒感染引起的宿主转录免疫应答的类型或时间的显著异质性,与疾病的持续时间无关。特别是,他们认为,如果血液室中的转录事件有助于毛细血管渗漏导致低血容量性休克,它们发生在心血管失代偿之前,这一发现对该综合征的合理辅助治疗具有意义。
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.
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