Holley-Guthrie E A, Quinlivan E B, Mar E C, Kenney S
Lineberger Cancer Research Center, University of North Carolina, Chapel Hill 27599-7295.
J Virol. 1990 Aug;64(8):3753-9. doi: 10.1128/JVI.64.8.3753-3759.1990.
The Epstein-Barr virus early antigen diffuse component (EA-D) is essential for Epstein-Barr virus DNA polymerase activity, and its activity is suppressed during latent infection. We investigated the regulation of the promoter (BMRF1) for this early gene by studying its responsiveness in vitro to two immediate-early viral transactivators, BZLF1 (Z) and BRLF1 (R), focusing on the differences in response in lymphoid cells and epithelial cells. In lymphoid cells, Z or R alone produced only small increases in EA-D promoter activity, whereas both transactivators together produced a large stimulatory effect. In epithelial cells, the Z transactivator alone produced maximal stimulation of the EA-D promoter; the effect of R and Z together was no greater than that of Z alone. Deletional analysis and site-directed mutagenesis of the EA-D promoter demonstrated that in epithelial cells the potential AP-1 binding site plays an essential role in Z responsiveness, although sequences further upstream are also important. In lymphoid cells, only the upstream sequences are required for transactivation by the Z/R combination, and the AP-1 site is dispensable. These data suggest that EA-D (BMRF1) promoter regulation by Z and R is cell type specific and appears to involve different mechanisms in each cell type.
爱泼斯坦-巴尔病毒早期抗原弥散成分（EA-D）对爱泼斯坦-巴尔病毒DNA聚合酶活性至关重要，且其活性在潜伏感染期间受到抑制。我们通过研究该早期基因启动子（BMRF1）在体外对两种即刻早期病毒反式激活因子BZLF1（Z）和BRLF1（R）的反应性来探究其调控机制，重点关注淋巴细胞和上皮细胞中反应的差异。在淋巴细胞中，单独的Z或R仅使EA-D启动子活性有小幅增加，而两种反式激活因子共同作用则产生较大的刺激作用。在上皮细胞中，单独的Z反式激活因子对EA-D启动子产生最大刺激；R和Z共同作用的效果不大于单独Z的作用。对EA-D启动子的缺失分析和定点诱变表明，在上皮细胞中，潜在的AP-1结合位点在Z反应性中起关键作用，尽管更上游的序列也很重要。在淋巴细胞中，Z/R组合反式激活仅需要上游序列，AP-1位点可有可无。这些数据表明，Z和R对EA-D（BMRF1）启动子的调控具有细胞类型特异性，且在每种细胞类型中似乎涉及不同机制。
