Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses.
Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses.
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DOI：
10.1371/journal.pbio.2004086
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发表时间：
2017-12
期刊：
影响因子：
9.8
通讯作者：
Palmarini M
中科院分区：
文献类型：
--
作者：
Shaw AE;Hughes J;Gu Q;Behdenna A;Singer JB;Dennis T;Orton RJ;Varela M;Gifford RJ;Wilson SJ;Palmarini M
I型干扰素（IFN）介导的宿主先天免疫反应以及由此产生的数百种干扰素刺激基因（ISGs）的上调，为病毒感染提供了直接屏障。对I型“干扰素”的研究主要是在单一物种水平上进行的，往往缺乏必要的力量来理解这一途径的关键进化特征。在这里，我们使用一个单一的实验平台，确定了多种脊椎动物物种的干扰素特性，并开发了一个web服务器来挖掘数据集。该方法揭示了62个isg的保守“核心”，包括先前未与IFN相关的基因，强调了与这种抗病毒宿主反应相关的祖先功能。我们表明，基因扩增有助于干扰素系统的进化，干扰素是由谱系特异性压力形成的。因此，每种哺乳动物都拥有独特的isg基因库，包括所有哺乳动物共有的基因和其他特定物种或系统发育谱系特有的基因。对IFN通常下调的基因的分析表明，转录的表观遗传调控是IFN反应的一个基本方面。我们的研究为科学界提供了一个资源，突出了I型IFN反应的关键范例。I型干扰素（IFN）反应是在被感染细胞感知到传入的病原体时触发的，并导致数百种干扰素刺激基因（isg，统称为“干扰素”）的表达。对干扰素的研究主要是在人类细胞中进行的，因此往往缺乏理解这一关键途径的比较进化方面的能力。在这项研究中，我们使用一个单一的实验框架对几种动物物种（包括人类）的干扰素进行了表征。这种方法使我们能够确定先天免疫系统的基本特性。特别是，我们揭示了62个“核心”isg，在所有脊椎动物中都对IFN响应上调，突出了IFN系统的祖先功能。此外，我们发现许多受IFN反应抑制的基因通常是细胞转录的调节因子。由多个物种共享的isg比其他基因更倾向于在基因组中存在多个拷贝。重要的是，我们观察到基因在进化过程中以isg的形式出现。因此，每个动物物种都拥有独特的isg序列，包括核心基因和谱系特异性基因。总的来说，我们的数据提供了一个框架，在这个框架上可以测试干扰素反应在病原体出现和跨物种传播中的作用。
The host innate immune response mediated by type I interferon (IFN) and the resulting up-regulation of hundreds of interferon-stimulated genes (ISGs) provide an immediate barrier to virus infection. Studies of the type I ‘interferome’ have mainly been carried out at a single species level, often lacking the power necessary to understand key evolutionary features of this pathway. Here, using a single experimental platform, we determined the properties of the interferomes of multiple vertebrate species and developed a webserver to mine the dataset. This approach revealed a conserved ‘core’ of 62 ISGs, including genes not previously associated with IFN, underscoring the ancestral functions associated with this antiviral host response. We show that gene expansion contributes to the evolution of the IFN system and that interferomes are shaped by lineage-specific pressures. Consequently, each mammal possesses a unique repertoire of ISGs, including genes common to all mammals and others unique to their specific species or phylogenetic lineages. An analysis of genes commonly down-regulated by IFN suggests that epigenetic regulation of transcription is a fundamental aspect of the IFN response. Our study provides a resource for the scientific community highlighting key paradigms of the type I IFN response. The type I interferon (IFN) response is triggered upon sensing of an incoming pathogen in an infected cell and results in the expression of hundreds of IFN-stimulated genes (ISGs, collectively referred to as ‘the interferome’). Studies on the interferome have been carried out mainly in human cells and therefore often lack the power to understand comparative evolutionary aspects of this critical pathway. In this study, we characterized the interferome in several animal species (including humans) using a single experimental framework. This approach allowed us to identify fundamental properties of the innate immune system. In particular, we revealed 62 ‘core’ ISGs, up-regulated in response to IFN in all vertebrates, highlighting the ancestral functions of the IFN system. In addition, we show that many genes repressed by the IFN response normally function as regulators of cell transcription. ISGs shared by multiple species have a higher propensity than other genes to exist as multiple copies in the genome. Importantly, we observed that genes have arisen as ISGs throughout evolution. Hence, every animal species possesses a unique repertoire of ISGs that includes core and lineage-specific genes. Collectively, our data provide a framework on which it will be possible to test the role of the IFN response in pathogen emergence and cross-species transmission.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
鹅MX和OASL在I型，II和III型干扰素与新兴新兴禽流病毒的抗病毒作用中起着至关重要的作用。
影响因子：
7.3
作者：
Chen S;Zhang W;Wu Z;Zhang J;Wang M;Jia R;Zhu D;Liu M;Sun K;Yang Q;Wu Y;Chen X;Cheng A
通讯作者：
Cheng A
影响因子：
4
作者：
Kadota, Shinichi;Nagata, Kyosuke
通讯作者：
Nagata, Kyosuke
影响因子：
14.9
作者：
Kambara H;Niazi F;Kostadinova L;Moonka DK;Siegel CT;Post AB;Carnero E;Barriocanal M;Fortes P;Anthony DD;Valadkhan S
通讯作者：
Valadkhan S
影响因子：
3.2
作者：
Erath, Sonja;Groettrup, Marcus
通讯作者：
Groettrup, Marcus