Glucocorticoids facilitate the transcription from the human cytomegalovirus major immediate early promoter in glucocorticoid receptor- and nuclear factor-I-like protein-dependent manner.
Glucocorticoids facilitate the transcription from the human cytomegalovirus major immediate early promoter in glucocorticoid receptor- and nuclear factor-I-like protein-dependent manner.
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糖皮质激素以糖皮质激素受体和核因子 I 样蛋白依赖性方式促进人巨细胞病毒主要立即早期启动子的转录。
DOI：
10.1016/j.bbrc.2015.01.091
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Yoshikawa H.
中科院分区：
文献类型：
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作者：
Inoue-Toyoda M;Kato K;Nagata K;Yoshikawa H.
人巨细胞病毒(HCMV)是一种在健康人中常见且通常无症状的病原体。HCMV产生性感染的启动依赖于主要即刻早期(MIE)基因的表达。人巨细胞病毒mie基因的转录受多种转录因子的调控。此前有报道称，生殖性巨细胞病毒感染可能是由血浆羟皮质激素水平升高引发的。然而，MIE基因的转录是否受糖皮质激素的直接调控目前还知之甚少。在这里，我们发现地塞米松(DEX)是一种人工合成的糖皮质激素，它通过MIE启动子和增强子以糖皮质激素受体(GR)依赖的方式促进HCMV mie基因的转录。通过竞争性EMSA和报告分析，我们发现一个类似NF-I的蛋白参与了DEX介导的MIE启动子的转录激活。因此，这项研究支持这样一种观点，即妊娠晚期羟皮质激素水平的增加重新激活了潜伏状态下的HCMV病毒的产生。
Human cytomegalovirus (HCMV) is a common and usually asymptomatic virus agent in healthy individuals. Initiation of HCMV productive infection depends on expression of the major immediate early (MIE) genes. The transcription of HCMV MIE genes is regulated by a diverse set of transcription factors. It was previously reported that productive HCMV infection is triggered probably by elevation of the plasma hydroxycorticoid level. However, it is poorly understood whether the transcription of MIE genes is directly regulated by glucocorticoid. Here, we found that the dexamethasone (DEX), a synthetic glucocorticoid, facilitates the transcription of HCMV MIE genes through the MIE promoter and enhancer in a glucocorticoid receptor (GR)-dependent manner. By competitive EMSA and reporter assays, we revealed that an NF-I like protein is involved in DEX-mediated transcriptional activation of the MIE promoter. Thus, this study supports a notion that the increased level of hydroxycorticoid in the third trimester of pregnancy reactivates HCMV virus production from the latent state.