Hata N, Sato M, Takaoka A, Asagiri M, Tanaka N, Taniguchi T
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Biochem Biophys Res Commun. 2001 Jul 13;285(2):518-25. doi: 10.1006/bbrc.2001.5159.
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.
在病毒感染的细胞中高效诱导干扰素-α/β基因是先天免疫的核心事件，其中转录因子IRF-7与IRF-3共同发挥关键作用。与IRF-3不同，IRF-7寿命短暂，其基因表达依赖于干扰素-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干扰素-α/β基因诱导的正反馈调节至关重要。在此，我们提供证据表明，未感染细胞中组成性的、不依赖IRF-3/IRF-7的干扰素-α/β产生对于设定IRF-7表达水平至关重要，这决定了病毒感染时正反馈机制是否能有效运作。事实上，脾细胞比成纤维细胞更依赖这一机制；阻断IRF-7诱导途径比引入IRF-3无效突变更严重地损害干扰素-α/β基因诱导。因此，组成性的干扰素-α/β信号为IRF-7介导的病毒感染时自身产生增强提供了基础。
