Kanda K, Kempkes B, Bornkamm G W, von Gabain A, Decker T
Vienna Biocenter, Institute for Microbiology and Genetics, University of Vienna, Austria.
Biol Chem. 1999 Feb;380(2):213-21. doi: 10.1515/BC.1999.029.
Epstein-Barr virus nuclear antigen 2 (EBNA2), a protein involved in cell transformation, interferes with the cellular response to type I interferons (IFN-alpha/beta). We investigated the function of conditionally expressed EBNA2 in the context of the IFN response in Burkitt's lymphoma cell lines. Expression of EBNA2 led to the transcriptional activation of both endogenous or transfected IFN-stimulated genes (ISGs), genes which contain within their promoters either the interferon-stimulated response element (ISRE) or the gamma interferon activation site (GAS). In search of a molecular mechanism for the transcriptional induction of ISGs, we observed an EBNA2-dependent synthesis of IFN-beta mRNA at low levels and the secretion of low amounts of IFN. A transfected IFN-beta promoter responded to EBNA2 activation, and a sequence closely resembling a RBP-Jkappa binding site was pinpointed as a potential target of EBNA2 activity. EBNA2-dependent transcriptional induction of the IFN-beta promoter occurred in EBV-negative Burkitt's lymphoma cells, indicating that other EBV genes were not required for the induction of IFN-beta synthesis.
爱泼斯坦-巴尔病毒核抗原2（EBNA2）是一种参与细胞转化的蛋白质，它会干扰细胞对I型干扰素（IFN-α/β）的反应。我们在伯基特淋巴瘤细胞系的IFN反应背景下研究了条件表达的EBNA2的功能。EBNA2的表达导致内源性或转染的干扰素刺激基因（ISG）转录激活，这些基因在其启动子内含有干扰素刺激反应元件（ISRE）或γ干扰素激活位点（GAS）。为了寻找ISG转录诱导的分子机制，我们观察到低水平的EBNA2依赖性IFN-β mRNA合成以及少量IFN的分泌。转染的IFN-β启动子对EBNA2激活有反应，并且一个与RBP-Jκ结合位点非常相似的序列被确定为EBNA2活性的潜在靶点。EBNA2依赖性的IFN-β启动子转录诱导发生在EBV阴性的伯基特淋巴瘤细胞中，这表明诱导IFN-β合成不需要其他EBV基因。
