Identification of host genes leading to West Nile virus encephalitis in mice brain using RNA-seq analysis.
Identification of host genes leading to West Nile virus encephalitis in mice brain using RNA-seq analysis.
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使用RNA-seq分析鉴定导致小鼠脑中西尼罗河病毒脑炎的宿主基因。
DOI：
10.1038/srep26350
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发表时间：
2016-05-23
影响因子：
4.6
通讯作者：
Nerurkar VR
中科院分区：
文献类型：
--
作者：
Kumar M;Belcaid M;Nerurkar VR
不同的宿主反应可能是西尼罗河病毒（WNV）NY 99（致病性）和WNV Eg 101（非致病性）毒株不同病理的关键决定因素。我们采用RNA-seq技术分析WNV感染小鼠脑中的整体差异基因表达，并确定导致致死性脑炎的宿主细胞因子。我们确定了1,400和278个转录本，分别在WNV NY 99和WNV Eg 101感染后差异表达，147个基因是两种病毒感染共有的。在两种病毒感染中上调的基因主要与干扰素信号有关。与炎症和细胞死亡/凋亡相关的基因仅在WNV NY 99感染后表达。我们证明了关键模式识别受体激活的差异导致了独特的先天免疫特征的诱导，这与干扰素和炎症反应的诱导相对应。差异表达基因的通路分析表明，在WNV NY 99感染后，TREM-1介导的Toll样受体激活导致高炎症反应。总之，我们已经确定了对WNV NY 99和WNV Eg 101感染的共同和特异性反应，以及与可能成为治疗靶点的潜在感染抗性相关的基因。
Differential host responses may be critical determinants of distinct pathologies of West Nile virus (WNV) NY99 (pathogenic) and WNV Eg101 (non-pathogenic) strains. We employed RNA-seq technology to analyze global differential gene expression in WNV-infected mice brain and to identify the host cellular factors leading to lethal encephalitis. We identified 1,400 and 278 transcripts, which were differentially expressed after WNV NY99 and WNV Eg101 infections, respectively, and 147 genes were common to infection with both the viruses. Genes that were up-regulated in infection with both the viruses were mainly associated with interferon signaling. Genes associated with inflammation and cell death/apoptosis were only expressed after WNV NY99 infection. We demonstrate that differences in the activation of key pattern recognition receptors resulted in the induction of unique innate immune profiles, which corresponded with the induction of interferon and inflammatory responses. Pathway analysis of differentially expressed genes indicated that after WNV NY99 infection, TREM-1 mediated activation of toll-like receptors leads to the high inflammatory response. In conclusion, we have identified both common and specific responses to WNV NY99 and WNV Eg101 infections as well as genes linked to potential resistance to infection that may be targets for therapeutics.