Differential viral induction of distinct interferon-α genes by positive feedback through interferon regulatory factor-7
Differential viral induction of distinct interferon-α genes by positive feedback through interferon regulatory factor-7
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DOI：
10.1093/emboj/17.22.6660
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发表时间：
1998-11-16
期刊：
影响因子：
11.4
通讯作者：
Levy, DE
中科院分区：
文献类型：
--
作者：
Marié, I;Durbin, JE;Levy, DE
干扰素（IFN）基因是哺乳动物细胞对病毒感染最早的转录反应之一。尽管 IFN β 基因的调控已得到很好的表征，但 IFN α 基因大家族的诱导仍不清楚。我们报告 IFN α 基因可分为两类：立即早期反应基因 (IFN α 4)，其被快速诱导，不需要持续的蛋白质合成；一组显示延迟诱导的基因，至少由 IFN α 2、5、6 和 8 组成，其诱导速度较慢，需要细胞蛋白质合成。诱导延迟基因集必须合成的一种蛋白质是 IFN 本身，大概是 IFN α 4 或 IFN β，它通过 IFN 受体刺激 Jak-Stat 通路，导致转录因子干扰素刺激基因因子 3 (ISGF3) 的激活。通过该正反馈环路诱导的 IFN 刺激基因包括 IFN 调节因子 (IRF) 蛋白、IRF7、IRF7 蛋白响应 IFN 的诱导及其随后的激活。延迟的 IFN α 基因组的诱导需要响应病毒特异性信号的磷酸化，涉及两个 C 末端丝氨酸残基。
Interferon (IFN) genes are among the earliest transcriptional responses to virus infection of mammalian cells. Although the regulation of the IFN beta gene has been well characterized, the induction of the large family of IFN alpha genes has remained obscure, We report that the IFN alpha genes can be divided into two groups: an immediate-early response gene (IFN alpha 4) which is induced rapidly and without the need for ongoing protein synthesis; and a set of genes that display delayed induction, consisting of at least IFN alpha 2, 5, 6 and 8, which are induced more slowly and require cellular protein synthesis. One protein that must be synthesized for induction of the delayed gene set is IFN itself, presumably IFN alpha 4 or IFN beta, which stimulates the Jak-Stat pathway through the IFN receptor, resulting in activation of the transcription factor interferon-stimulated gene factor 3 (ISGF3), Among the IFN-stimulated genes induced through this positive feedback loop is the IFN regulatory factor (IRF) protein, IRF7, Induction of IRF7 protein in response to IFN and its subsequent activation by phosphorylation in response to virus-specific signals, involving two C-terminal serine residues, are required for induction of the delayed IFN alpha gene set.