Departments of Pediatrics and Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, United States; Department of Molecular Biology, National Research Center, Dokki, Cairo, Egypt.
Departments of Pediatrics and Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, United States.
Virology. 2014 Jan 20;449:244-53. doi: 10.1016/j.virol.2013.11.029. Epub 2013 Dec 12.
Several cellular transcription factors have been shown to be involved in IE62-mediated activation. The YY1 cellular transcription factor has activating and repressive effects on gene transcription. Analysis of the VZV genome revealed 19 postulated YY1 binding sites located within putative promoters of 16 VZV genes. Electrophoretic mobility shift assays (EMSA) confirmed the binding of YY1 to ORF10, ORF28/29 and gI promoters and the mutation of these binding sites inhibited YY1 binding and the promoter activation by IE62 alone or following VZV infection. Mutation of the ORF28/29 YY1 site in the VZV genome displayed insignificant influence on virus growth in melanoma cells; but it inhibited the virus replication significantly at day 5 and 6 post infection in HELF cells. This work suggests a novel role for the cellular factor YY1 in VZV replication through the mediation of IE62 activation of viral gene expression.
已有研究表明,几种细胞转录因子参与了 IE62 介导的激活。YY1 细胞转录因子对基因转录具有激活和抑制作用。对 VZV 基因组的分析表明,在 16 个 VZV 基因的推定启动子中,有 19 个假定的 YY1 结合位点。电泳迁移率变动分析(EMSA)证实 YY1 与 ORF10、ORF28/29 和 gI 启动子结合,并且这些结合位点的突变抑制了 IE62 单独或在 VZV 感染后结合和启动子的激活。VZV 基因组中 ORF28/29 YY1 位点的突变对黑色素瘤细胞中的病毒生长没有显著影响;但它显著抑制了 HELF 细胞中感染后第 5 天和第 6 天的病毒复制。这项工作表明,细胞因子 YY1 通过 IE62 激活病毒基因表达,在 VZV 复制中发挥了新的作用。