Distinctive Effects of the Epstein-Barr Virus Family of Repeats on Viral Latent Gene Promoter Activity and B-Lymphocyte Transformation
Distinctive Effects of the Epstein-Barr Virus Family of Repeats on Viral Latent Gene Promoter Activity and B-Lymphocyte Transformation
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DOI：
10.1128/jvi.01979-08
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发表时间：
2009-09-15
影响因子：
5.4
通讯作者：
Kanda, Teru
中科院分区：
文献类型：
--
作者：
Ali, Ahmed K. M.;Saito, Satoru;Kanda, Teru
EB病毒（EBV）是一种人类嗜B淋巴细胞γ疱疹病毒，其基因组中含有多个重复序列。一组被称为重复序列家族（FR）的重复序列包含病毒反式作用蛋白EBNA-1的多个结合位点。FR序列对于病毒基因组的维持和参与病毒潜伏基因表达的启动子的调节是重要的。据报道，具有推定二级结构的回文序列存在于EBV B 95 -8株基因组中FR的3'末端，并且该回文序列已从常用EBV小质粒的FR中缺失。我们首次克隆了含有全长FR的EBV B 95 -8 DNA片段，这使我们能够研究全长FR和缺失FR之间的功能差异。全长FR，像删除FR，作为病毒潜伏基因启动子的转录增强子，但反式激活显着衰减的情况下，全长FR。没有显着增强复制时，观察到删除FR被替换为全长FR在EBV微型质粒。相比之下，当同一组FR序列进行测试的背景下，完整的EBV基因组，全长FR导致更有效的B细胞转化比删除FR。我们建议，全长FR的存在有助于精确调节病毒潜伏启动子，并提高B细胞转化的效率。
The Epstein-Barr virus (EBV), a human B-lymphotropic gamma herpesvirus, contains multiple repetitive sequences within its genome. A group of repetitive sequences, known as the family of repeats (FR), contains multiple binding sites for the viral trans-acting protein EBNA-1. The FR sequences are important for viral genome maintenance and for the regulation of the promoter involved in viral latent gene expression. It has been reported that a palindromic sequence with a putative secondary structure exists at the 3' end of the FR in the genome of the EBV B95-8 strain and that this palindromic sequence has been deleted from the FR of the commonly used EBV miniplasmids. For the first time, we cloned an EBV B95-8 DNA fragment containing the full-length FR, which enabled us to examine the functional difference between full-length and deleted FRs. The full-length FR, like the deleted FR, functioned as a transcriptional enhancer of the viral latent gene promoter, but that transactivation was significantly attenuated in the case of the full-length FR. No significant enhancement of replication was observed when the deleted FR was replaced with the full-length FR in an EBV miniplasmid. By contrast, when the same set of FR sequences were tested in the context of the complete EBV genome, the full-length FR resulted in more-efficient B-cell transformation than the deleted FR. We propose that the presence of the full-length FR contributes to the precise regulation of the viral latent promoter and increases the efficiency of B-cell transformation.