Lysine residues K66, K109, and K110 in the bovine foamy virus transactivator protein are required for transactivation and viral replication
Lysine residues K66, K109, and K110 in the bovine foamy virus transactivator protein are required for transactivation and viral replication
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牛泡沫病毒反式激活蛋白中的赖氨酸残基 K66、K109 和 K110 是反式激活和病毒复制所必需的
DOI：
10.1007/s12250-015-3652-x
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发表时间：
2016-03
影响因子：
5.5
通讯作者：
Tan Juan
中科院分区：
文献类型：
--
作者：
Zhang Suzhen;Cui Xiaoxu;Li Jing;Liang Zhibin;Qiao Wentao;Tan Juan
牛泡沫病毒（BFV）是一种感染牛的复杂逆转录病毒。像所有逆转录病毒一样，BFV编码一种反激活子Tas蛋白（BTas），该蛋白可以增加病毒启动子的基因转录。BFV编码两个可以与bta相互作用的启动子，一个位于5'长末端重复序列（LTR）的保守启动子和一个独特的内部启动子（IP）。我们之前的研究表明，BTas在K66、K109和K110位点被p300乙酰化，这显著增强了BTas与DNA结合的能力。然而，这些残基对BFV复制是否重要尚未确定。因此，在本研究中，我们提供了BTas是BFV复制所必需的直接证据，并证明残基K66、K109和K110对BTas的功能和BFV复制至关重要。产生全长感染性克隆，这些克隆缺乏BTas或在第66、109和/或110位含有赖氨酸到精氨酸（K→R）突变。体内实验数据表明，bta中K→R在第66、109和110位的突变破坏了LTR和IP启动子的交换激活。此外，全长感染性克隆中的K→R突变降低了病毒蛋白的表达，三重突变和BTas的缺失完全消除了病毒的复制。综上所述，这些结果表明BTas蛋白的66,109和110位赖氨酸残基对BFV复制至关重要，并表明BTas乙酰化在调节病毒生命周期中可能起作用。
Bovine foamy virus (BFV) is a complex retrovirus that infects cattle. Like all retroviruses, BFV encodes a transactivator Tas protein (BTas) that increases gene transcription from viral promoters. BFV encodes two promoters that can interact with BTas, a conserved promoter in the 5' long terminal repeat (LTR) and a unique internal promoter (IP). Our previous study showed that BTas is acetylated by p300 at residues K66, K109, and K110, which markedly enhanced the ability of BTas to bind to DNA. However, whether these residues are important for BFV replication was not determined. Therefore, in this study we provide direct evidence that BTas is required for BFV replication and demonstrate that residues K66, K109, and K110 are critical for BTas function and BFV replication. Full-length infectious clones were generated, which were BTas deficient or contained lysine to arginine (K→R) mutations at position 66, 109, and/or 110.In vivodata indicated that K→R mutations at positions 66, 109, and 110 in BTas impaired transactivation of both the LTR and IP promoters. In addition, the K→R mutations in full-length infectious clones reduced expression of viral proteins, and the triple mutant and BTas deletion completely abrogated viral replication. Taken together, these results indicate that lysine residues at positions 66, 109, and 110 in the BTas protein are crucial for BFV replication and suggest a potential role for BTas acetylation in regulating the viral life cycle.
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影响因子：
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作者：
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