Fish virus-induced interferon exerts antiviral function through Stat1 pathway
Fish virus-induced interferon exerts antiviral function through Stat1 pathway
复制标题
鱼病毒诱导的干扰素通过Stat1途径发挥抗病毒功能
DOI：
10.1016/j.molimm.2010.05.282
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发表时间：
2010-08-01
影响因子：
3.6
通讯作者：
Gui, Jian-Fang
中科院分区：
文献类型：
--
作者：
Yu, Fei-Fei;Zhang, Yi-Bing;Gui, Jian-Fang
病毒诱导的干扰素（virus-induced interferon，IFN）在多种鱼类中被发现，并显示出与哺乳动物I型IFN相似的抗病毒活性。然而，除了哺乳动物IFN系统外，IFN信号通路在很大程度上仍不清楚。（Carassius auratus L）IFN对草鱼出血症病毒（Grass carp hemorrhagic virus，GCHV）感染具有较强的抗病毒活性，并能介导Poly I C-诱导的抗病毒反应与其诱导一组干扰素刺激基因（ISGs）的能力相关。野生型Stat 1的过表达显著增强了IFN对ISGs表达和病毒感染抑制的作用，而Stat 1的显性负突变体（Stat 1-Delta C），其缺少C-末端转录激活结构域（STAT 1）抑制IFN的抗病毒活性并减少ISG的表达，这表明鱼IFN通过Stat 1途径诱导ISG的表达和宿主抗病毒应答，这使人联想到哺乳动物IFN的途径。这些结果为鱼类和哺乳动物之间存在进化上保守的Stat 1途径提供了强有力的证据，这是鱼类病毒诱导的IFN抗病毒反应所不可或缺的（C）2010 Elsevier Ltd版权所有
Virus-Induced interferons (IFNs) have been identified in various fish species and display antiviral activities similar to mammalian type I IFNs However apart from the mammalian IFN system the IFN signaling pathway remains largely unknown Using transient transfection and recombinant protein we are reporting in this study that a crucian carp (Carassius auratus L) IFN exhibits strong antiviral activity against grass carp hemorrhagic virus (GCHV) infection and also mediates Poly I C-Induced antiviral response which correlates with its ability to Induce a set of IFN-stimulated genes (ISGs) Strikingly overexpression of wild-type Stat1 increases the effects of IFN on both the expression of ISGs and the inhibition of virus infection whereas a dominant negative mutant of Stat1 (Stat1-Delta C) which lacks of the C-terminal transcriptional activation domain (TAD) inhibits the antiviral activity of IFN and reduces the expression of ISGs demonstrating that fish IFN induces the expression of ISGs and host antiviral response through Stat1 pathway reminiscent that of mammalian IFNs Significantly unlike mammalian type I IFNs recombinant fish IFN is able to upregulate IFN itself which is enhanced by overexpression of Stat1 but impaired by knockdown of Stat1 indicating a positive feedback loop in regulation of IFN itself These results provide strong evidence for the existence of an evolutionary conserved Stat1 pathway between fish and mammals which is indispensable for fish virus-induced IFN antiviral response (C) 2010 Elsevier Ltd All rights reserved