Important role of N108 residue in binding of bovine foamy virus transactivator Tas to viral promoters.
Important role of N108 residue in binding of bovine foamy virus transactivator Tas to viral promoters.
复制标题
N108残基在牛泡沫病毒反式激活子Tas与病毒启动子结合中的重要作用
DOI：
10.1186/s12985-016-0579-2
复制
发表时间：
2016-06-30
期刊：
影响因子：
4.8
通讯作者：
Tan J
中科院分区：
文献类型：
--
作者：
Bing T;Zhang S;Liu X;Liang Z;Shao P;Zhang S;Qiao W;Tan J
牛泡沫病毒(Bovine Foamy Virus，BFV)编码反式激活因子BTAS，通过与长末端重复序列启动子和内部启动子结合，增强病毒基因转录。在这项研究中，我们研究了两个相似的BFV全长DNA克隆PBS-BFV-Y和PBS-BFV-B的不同复制能力。结果对几个嵌合克隆的功能分析表明，病毒基因组的C末端区域是造成这种差异的主要原因。此外，位于该C末端区域的BTAS-B显示出比BTAS-Y高20倍的反式激活活性。序列比对表明，这两个序列仅在108位氨基酸不同，BTAS-B在该位置含有N108，BTAS-Y在该位置含有D108。突变研究结果表明，N108残基对于BTAS与病毒启动子的结合是重要的。此外，PBS-BFV-B的N108D突变使病毒的复制能力降低了约1.5倍。结论N108残基对BTAS与BFV启动子的结合具有重要作用，在BFV复制中起重要作用。这些发现不仅促进了我们对BTAS反式激活机制的理解，而且也突显了某些序列多态在调节分离的BFV克隆复制能力方面的重要性。
BackgroundBovine foamy virus (BFV) encodes the transactivator BTas, which enhances viral gene transcription by binding to the long terminal repeat promoter and the internal promoter. In this study, we investigated the different replication capacities of two similar BFV full-length DNA clones, pBS-BFV-Y and pBS-BFV-B.ResultsHere, functional analysis of several chimeric clones revealed a major role for the C-terminal region of the viral genome in causing this difference. Furthermore, BTas-B, which is located in this C-terminal region, exhibited a 20-fold higher transactivation activity than BTas-Y. Sequence alignment showed that these two sequences differ only at amino acid 108, with BTas-B containing N108 and BTas-Y containing D108 at this position. Results of mutagenesis studies demonstrated that residue N108 is important for BTas binding to viral promoters. In addition, the N108D mutation in pBS-BFV-B reduced the viral replication capacity by about 1.5-fold.ConclusionsOur results suggest that residue N108 is important for BTas binding to BFV promoters and has a major role in BFV replication. These findings not only advances our understanding of the transactivation mechanism of BTas, but they also highlight the importance of certain sequence polymorphisms in modulating the replication capacity of isolated BFV clones.