title: Glucocorticoids facilitate the transcription from the human cytomegalovirus major immediate early promoter in glucocorticoid receptor- and nuclear factor-I-like protein-dependent manner.
abstract: 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.
authors: Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
authors: Maki
authors: M
authors: Inoue-Toyoda
authors: Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan; Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
authors: Kohsuke
authors: K
authors: Kato
authors: University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan. Electronic address: knagata@md.tsukuba.ac.jp.
authors: Kyosuke
authors: K
authors: Nagata
authors: Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan; Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
authors: Hiroyuki
authors: H
authors: Yoshikawa
mesh_terms: D001483:Base Sequence; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics* / Q000472:pathogenicity; D003907:Dexamethasone / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D017781:Genes, Immediate-Early; D005938:Glucocorticoids / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects / Q000821:virology; D006801:Humans; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D020218:Response Elements / Q000235:genetics
chemical_list: D005938:Glucocorticoids; D051839:NFI Transcription Factors; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone
keywords: Dexamethasone (DEX); Glucocorticoid; Glucocorticoid receptor (GR); Human cytomegalovirus (HCMV); Major immediate early (MIE) promoter; Nuclear factor-I (NF-I)