Ousman Shalina S, Wang Jianping, Campbell Iain L
School of Molecular and Microbial Biosciences, G08 Maze Crescent, University of Sydney, New South Wales 2006, Australia.
J Virol. 2005 Jun;79(12):7514-27. doi: 10.1128/JVI.79.12.7514-7527.2005.
Interferon regulatory factors (IRFs) are a family of transcription factors involved in the regulation of the interferons (IFNs) and other genes that may have an essential role in antiviral defense in the central nervous system, although this is currently not well defined. Therefore, we examined the regulation of IRF gene expression in the brain during viral infection. Several IRF genes (IRF-2, -3, -5, -7, and -9) were expressed at low levels in the brain of uninfected mice. Following intracranial infection with lymphocytic choriomeningitis virus (LCMV), expression of the IRF-7 and IRF-9 genes increased significantly by day 2. IRF-7 and IRF-9 gene expression in the brain was widespread at sites of LCMV infection, with the highest levels in infiltrating mononuclear cells, microglia/macrophages, and neurons. IRF-7 and IRF-9 gene expression was increased in LCMV-infected brain from IFN-gamma knockout (KO) but not IFN-alpha/betaR KO animals. In the brain, spleen, and liver or cultured glial and spleen cells, IRF-7 but not IRF-9 gene expression increased with delayed kinetics in the absence of STAT1 but not STAT2 following LCMV infection or IFN-alpha treatment, respectively. The stimulation of IRF-7 gene expression by IFN-alpha in glial cell culture was prevented by cycloheximide. Thus, (i) many of the IRF genes were expressed constitutively in the mouse brain; (ii) the IRF-7 and IRF-9 genes were upregulated during viral infection, a process dependent on IFN-alpha/beta but not IFN-gamma; and (iii) IRF-7 but not IRF-9 gene expression can be stimulated in a STAT1-independent but STAT2-dependent fashion via unidentified indirect pathways coupled to the activation of the IFN-alpha/beta receptor.
干扰素调节因子（IRFs）是一类转录因子，参与干扰素（IFNs）及其他基因的调控，这些基因可能在中枢神经系统的抗病毒防御中发挥重要作用，尽管目前对此尚未明确界定。因此，我们研究了病毒感染期间大脑中IRF基因表达的调控情况。几种IRF基因（IRF - 2、- 3、- 5、- 7和- 9）在未感染小鼠的大脑中表达水平较低。经淋巴细胞性脉络丛脑膜炎病毒（LCMV）颅内感染后，到第2天IRF - 7和IRF - 9基因的表达显著增加。大脑中IRF - 7和IRF - 9基因的表达在LCMV感染部位广泛存在，在浸润的单核细胞、小胶质细胞/巨噬细胞和神经元中水平最高。在LCMV感染的大脑中，IFN - γ基因敲除（KO）小鼠的IRF - 7和IRF - 9基因表达增加，而IFN - α/βR KO小鼠则未增加。在大脑、脾脏和肝脏或培养的神经胶质细胞和脾细胞中，LCMV感染或IFN - α处理后，在缺乏STAT1而非STAT2的情况下，IRF - 7而非IRF - 9基因的表达分别以延迟的动力学增加。在神经胶质细胞培养中，放线菌酮可阻止IFN - α对IRF - 7基因表达的刺激。因此，（i）许多IRF基因在小鼠大脑中组成性表达；（ii）IRF - 7和IRF - 9基因在病毒感染期间上调，这一过程依赖于IFN - α/β而非IFN - γ；（iii）IRF - 7而非IRF - 9基因的表达可通过与IFN - α/β受体激活相关的未知间接途径以不依赖STAT1但依赖STAT2的方式被刺激。
