CONSTITUTIVE AND RETINOIC ACID INDUCIBLE EXPRESSION OF CYTOMEGALOVIRUS IMMEDIATE-EARLY GENES IN HUMAN TERATOCARCINOMA CELLS

CONSTITUTIVE AND RETINOIC ACID INDUCIBLE EXPRESSION OF CYTOMEGALOVIRUS IMMEDIATE-EARLY GENES IN HUMAN TERATOCARCINOMA CELLS
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DOI:
10.1128/jvi.58.2.434-440.1986
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发表时间:
1986-05-01
影响因子:
5.4
通讯作者:
HAYWARD, GS
HAYWARD, GS
中科院分区:
医学2区
文献类型:
--
作者:
LAFEMINA, R;HAYWARD, GS

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人畸胎瘤干细胞对人巨细胞病毒(HCMV)是不允许的,但在用视黄酸处理诱导分化后变得允许。我们表明,在未诱导的畸胎瘤干细胞,也在转化的人293细胞表达腺病毒E1 a基因产物,HCMV立即早期(IE)68,000-分子量多肽(68 K多肽)没有表达,因此输入病毒基因组没有复制。然而,在畸胎癌细胞分化后,诱导HCMV IE 68 K多肽的合成,并发生病毒DNA复制。与我们对HCMV的观察相反,猴巨细胞病毒(SCMV)显示其类似IE 94 K多肽的组成型表达,并且输入的SCMV基因组在未诱导的干细胞和293细胞中复制。由于很少,如果有的话,HCMV IE RNA在人畸胎瘤或293细胞感染后IE条件下检测,我们建议,在这些细胞中发生的perceptin的直接转录阻断。在SCMV IE 94 K多肽基因的启动子中而不是在HCMV IE 68 K多肽基因的启动子中存在与核因子1蛋白结合的串联重复序列,这可能允许在转化细胞中表达猿猴而不是人IE基因产物。
Human teratocarcinoma stem cells are nonpermissive for human cytomegalovirus (HCMV) but become permissive after being induced to differentiate by treatment with retinoic acid. We show that in uninduced teratocarcinoma stem cells, and also in transformed human 293 cells expressing adenovirus E1a gene products, the HCMV immediate-early (IE) 68,000-molecular-weight polypeptide (68K polypeptide) was not expressed, and consequently input viral genomes were not replicated. However, after differentiation of the teratocarcinoma cells, synthesis of the HCMV IE 68K polypeptide was induced, and viral DNA replication occurred. In contrast to our observations for HCMV, simian cytomegalovirus (SCMV) displayed constitutive expression of its analogous IE 94K polypeptide, and the input SCMV genomes were replicated in both uninduced stem cells and 293 cells. Since little, if any, HCMV IE RNA was detectable in human teratocarcinoma or 293 cells after infection under IE conditions, we suggest that a direct transcriptional block to permissivity occurs in these cells. The presence of tandemly repeated sequences which bind nuclear factor 1 protein in the promoter for the SCMV IE 94K polypeptide gene but not in the promoter for the HCMV IE 68K polypeptide gene may allow the expression of the simian but not of the human IE gene product in transformed cells.