Monick M M, Geist L J, Stinski M F, Hunninghake G W
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Am J Respir Cell Mol Biol. 1992 Sep;7(3):251-6. doi: 10.1165/ajrcmb/7.3.251.
Human cytomegalovirus (HCMV) is an important pathogen of the lung. We determined whether the HCMV immediate early genes (IE1 and IE2) can alter the regulation of the cellular immediate early genes (c-fos and c-myc). Plasmid constructs containing the promoter-regulatory regions c-myc or c-fos upstream of the reporter gene, chloramphemicol acetyl transferase, were co-transfected into T cells (Jurkat cells), monocytes/macrophages (THP-1 cells), or human fibroblast cells with plasmid constructs containing the promoter-regulatory region of the HCMV IE genes upstream of the bona fide IE1, IE2 or IE+2 genes; a plasmid that contained no IE coding region was used as a control. These studies show that both products of the HCMV IE genes markedly upregulated expression of the cellular c-fos and c-myc genes. The viral effects of individual proteins (IE1 or IE2) were dependent both on the promoter-regulatory region of the cellular gene and the cell type. In all cells, the combination of IE1 and IE2 further upregulated both cellular genes, suggesting a synergistic effect of IE1 with IE2. Both of the c-myc promoters (P1 and P2) were up-regulated by the HCMV IE gene products. IE1 and IE2 also upregulated the cells' endogenous c-myc and c-fos genes, as determined by amounts of the respective mRNAs. These studies show that HCMV can markedly alter cellular IE gene expression and that the effects of HCMV IE1 and IE2 proteins are dependent both on the promoter-regulatory region of the cellular gene and the type of cell in which the interaction occurs.
人巨细胞病毒（HCMV）是肺部的一种重要病原体。我们确定了HCMV立即早期基因（IE1和IE2）是否能改变细胞立即早期基因（c-fos和c-myc）的调控。将含有报告基因氯霉素乙酰转移酶上游c-myc或c-fos启动子调控区的质粒构建体，与含有HCMV IE基因启动子调控区且位于真正的IE1、IE2或IE+2基因上游的质粒构建体一起共转染到T细胞（Jurkat细胞）、单核细胞/巨噬细胞（THP-1细胞）或人成纤维细胞中；使用不含IE编码区的质粒作为对照。这些研究表明，HCMV IE基因的两种产物均显著上调细胞c-fos和c-myc基因的表达。单个蛋白（IE1或IE2）的病毒效应既取决于细胞基因的启动子调控区，也取决于细胞类型。在所有细胞中，IE1和IE2的组合进一步上调了这两种细胞基因，提示IE1与IE2存在协同效应。HCMV IE基因产物上调了c-myc的两个启动子（P1和P2）。通过各自mRNA的量确定，IE1和IE2也上调了细胞内源性c-myc和c-fos基因。这些研究表明，HCMV可显著改变细胞IE基因表达，且HCMV IE1和IE2蛋白的效应既取决于细胞基因的启动子调控区，也取决于发生相互作用的细胞类型。
