Constitutive IFN-α/β signal for efficient IFN-α/β gene induction by virus
Constitutive IFN-α/β signal for efficient IFN-α/β gene induction by virus
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DOI：
10.1006/bbrc.2001.5159
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发表时间：
2001-07-13
影响因子：
3.1
通讯作者：
Taniguchi, T
中科院分区：
文献类型：
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作者：
Hata, N;Sato, M;Taniguchi, T
在病毒感染的细胞中有效的IFN-α/β基因诱导是先天免疫的核心事件，其中转录因子IRF-7与IRF-3一起发挥关键作用。与IRF-3不同，IRF-7是短暂的，其基因表达依赖于IFN-α/β信号传导;因此，病毒感染期间IRF-7基因诱导的信号依赖性增强对于IFN-α/β基因诱导的正反馈调节至关重要。在这里，我们提供的证据表明，在未感染的细胞组成，IRF-3/IRF-7的IFN-α/β的独立生产是至关重要的设置IRF-7的表达水平，确定是否正反馈机制将有效地运作后病毒感染。事实上，脾细胞比成纤维细胞更依赖于这种机制;阻断IRF-7诱导途径比引入IRF-3无效突变更严重地损害IFN-α/β基因诱导。因此，组成型IFN-α/β信号为IRF-7介导的响应病毒感染的自身产生的增强提供了基础。(C)北京：科学出版社.
Efficient IFN-alpha/beta gene induction in virus-infected cells is an event central to innate immunity, in which the transcription factor IRF-7 plays a critical role together with IRF-3. Unlike IRF-3, IRF-7 is short-lived and its gene expression is dependent on IFN-alpha/beta signalling; hence, the signal-dependent enhancement of IRF-7 gene induction during viral infection is essential for positive-feedback regulation of IFN-alpha/beta gene induction. Here, we provide evidence that constitutive, IRF-3/IRF-7-independent production of IFN-alpha/beta in uninfected cells is critical for setting the IRF-7 expression levels, determining whether or not the positive-feedback mechanism will operate effectively upon viral infection. In fact, spleen cells are more dependent than fibroblasts on this mechanism; the IFN-alpha/beta gene induction is impaired more severely by blocking the IRF-7 induction pathway than by introducing an IRF-3 null mutation. Thus, the constitutive IFN-alpha/beta signal provides a foundation for the IRF-7-mediated enhancement of its own production in response to virus infection. (C) 2001 Academic Press.