Boomker Jasper M, The T Hauw, de Leij Lou F M H, Harmsen Martin C
Department of Pathology and Laboratory Medicine, Medical Biology Section, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Virus Res. 2006 Jun;118(1-2):196-200. doi: 10.1016/j.virusres.2005.12.011. Epub 2006 Jan 31.
The activation of the major immediate-early promoter (MIEP) is a key event in the cytomegalovirus replication cycle and is dependent on cellular transcription factors which are partially activated by viral proteins. Expression of the viral chemokine receptor homolog US28 results in constitutive activation of pro-inflammatory transcription factors that may be involved in the activation of the major immediate-early promoter/enhancer. Using reporter gene assays in human embryonic kidney cells, we found that US28 signaling was responsible for increased major immediate-early promoter/enhancer activity which was independent of beta-chemokine binding. Inhibition of nuclear factor-kappaB (NF-kappaB) only partially blocked the effect of US28, whereas treatment with a specific p38 mitogen activated kinase (MAPK) inhibitor fully abrogated the US28-induced enhancement of promoter activity. Our results suggest that during human cytomegalovirus (HCMV) infection, US28 in epithelial cells transactivates the major immediate-early promoter/enhancer via the activation of p38 MAPK and downstream signaling that partially involves NF-kappaB.
主要立即早期启动子（MIEP）的激活是巨细胞病毒复制周期中的关键事件，并且依赖于被病毒蛋白部分激活的细胞转录因子。病毒趋化因子受体同源物US28的表达导致促炎转录因子的组成性激活，这些转录因子可能参与主要立即早期启动子/增强子的激活。在人胚肾细胞中使用报告基因检测，我们发现US28信号传导导致主要立即早期启动子/增强子活性增加，这与β趋化因子结合无关。核因子-κB（NF-κB）的抑制仅部分阻断了US28的作用，而用特异性p38丝裂原活化蛋白激酶（MAPK）抑制剂处理则完全消除了US28诱导的启动子活性增强。我们的结果表明，在人巨细胞病毒（HCMV）感染期间，上皮细胞中的US28通过激活p38 MAPK和部分涉及NF-κB的下游信号传导来反式激活主要立即早期启动子/增强子。
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