The NS1 protein of influenza A virus suppresses interferon-regulated activation of antigen-presentation and immune-proteasome pathways
The NS1 protein of influenza A virus suppresses interferon-regulated activation of antigen-presentation and immune-proteasome pathways
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DOI：
10.1099/vir.0.032060-0
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发表时间：
2011-09-01
影响因子：
3.8
通讯作者：
Katze, Michael G.
中科院分区：
文献类型：
--
作者：
Tisoncik, Jennifer R.;Billharz, Rosalind;Katze, Michael G.
流感病毒的NS 1蛋白主要通过拮抗I型干扰素（IFN）应答来对抗宿主的抗病毒防御。N-末端dsRNA结合结构域和C-末端效应结构域都是在感染期间最佳抑制宿主应答所必需的。为了更好地了解NS 1效应域的调节作用，我们使用了一种NS 1截短的突变病毒，该病毒来源于人H1N1流感病毒分离株A/Texas/36/91（Tx/91），并评估了两种独立的人肺细胞培养模型的全局转录谱。相对于野生型Tx/91诱导的基因表达，NS 1突变体病毒诱导先天免疫基因的表达增强，特别是NF-κ B信号通路基因和IFN-α和IFN-β靶基因。我们查询了一个实验衍生的IFN基因集，以衡量特异性抑制NS 1的IFN应答基因的比例。我们表明，C-末端截短的NS 1突变病毒是有效地抑制干扰素调节的基因表达与抗原呈递和免疫蛋白酶体途径的激活。这是第一份报告整合基因组分析从两个独立的人类培养系统，包括原代肺细胞，使用遗传相似的H1N1流感病毒，不同的只是在NS 1蛋白的长度。
The NS1 protein of influenza virus counters host antiviral defences primarily by antagonizing the type I interferon (IFN) response. Both the N-terminal dsRNA-binding domain and the C-terminal effector domain are required for optimal suppression of host responses during infection. To better understand the regulatory role of the NS1 effector domain, we used an NS1-truncated mutant virus derived from human H1N1 influenza isolate A/Texas/36/91 (Tx/91) and assessed global transcriptional profiles from two independent human lung cell-culture models. Relative to the wild-type Tx/91-induced gene expression, the NS1 mutant virus induced enhanced expression of innate immune genes, specifically NF-kappa B signalling-pathway genes and IFN-alpha and -beta target genes. We queried an experimentally derived IFN gene set to gauge the proportion of IFN-responsive genes that are suppressed specifically by NS1. We show that the C-terminally truncated NS1 mutant virus is less efficient at suppressing IFN-regulated gene expression associated with activation of antigen-presentation and immune-proteasome pathways. This is the first report integrating genomic analysis from two independent human culture systems, including primary lung cells, using genetically similar H1N1 influenza viruses that differ only in the length of the NS1 protein.