Chevallier-Greco A, Gruffat H, Manet E, Calender A, Sergeant A
Laboratoire de Virologie Moléculaire, Ecole Normale Supérieure de Lyon, France.
J Virol. 1989 Feb;63(2):615-23. doi: 10.1128/JVI.63.2.615-623.1989.
The Epstein-Barr virus (EBV) DR promoter is located upstream of the PstI repeats, and besides the TATA box, it contains two cis-acting regulatory elements. One of them has enhancer properties. To define more precisely the functional region(s) in the DR enhancer, we generated 5' and 3' deletion mutants. These deletion mutants, which were transfected into various recipient cells of different origins, allowed us to identify two functionally distinct domains, A and B. Domain A was constitutively active in all cell lines tested, except in lymphoid B cells. Domain B was active in lymphoid B cells, and its activity required both EB1 (the BZLF1-encoded EBV trans-acting factor) and the presence of the EBV genome. This suggested that an EBV-encoded, EB1-inducible factor was activating the enhancer B domain. In effect, the B domain was trans-activated by R, an EBV early product encoded by the open reading frame BRLF1, and the activation by R occurred in epithelial, fibroblastic, and lymphoid cells. The R-responsive element has been reduced to 28 base pairs containing the double palindromic sequence TTGTCCCGTGGACAATGTCC. Both domains A and B act by increasing the initiation of specific RNAs.
爱泼斯坦-巴尔病毒（EBV）DR启动子位于PstI重复序列的上游，除TATA盒外，它还包含两个顺式作用调节元件。其中一个具有增强子特性。为了更精确地定义DR增强子中的功能区域，我们构建了5'和3'缺失突变体。将这些缺失突变体转染到不同来源的各种受体细胞中，使我们能够鉴定出两个功能不同的结构域，A和B。结构域A在所有测试的细胞系中均具有组成型活性，但在B淋巴细胞中除外。结构域B在B淋巴细胞中具有活性，其活性需要EB1（BZLF1编码的EBV反式作用因子）和EBV基因组的存在。这表明一种EBV编码的、EB1诱导型因子正在激活增强子B结构域。实际上，B结构域被R反式激活，R是由开放阅读框BRLF1编码的一种EBV早期产物，并且R的激活发生在上皮细胞、成纤维细胞和淋巴细胞中。R反应元件已被缩减为包含双回文序列TTGTCCCGTGGACAATGTCC的28个碱基对。结构域A和B均通过增加特定RNA的起始发挥作用。
