Stimulation of bovine herpesvirus-1 productive infection by the adenovirus E1A gene and a cell cycle regulatory gene, E2F-4
Stimulation of bovine herpesvirus-1 productive infection by the adenovirus E1A gene and a cell cycle regulatory gene, E2F-4
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DOI：
10.1099/vir.0.18915-0
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发表时间：
2003-04-01
影响因子：
3.8
通讯作者：
Jones, C
中科院分区：
文献类型：
--
作者：
Geiser, V;Jones, C
识别促进牛疱疹病毒-1(BHV-1)产生性感染的细胞基因是重要的，因为BHV-1是一种重要的牛病原体。以前的研究表明，BHV-1DNA除非与表达blCP0的质粒共转染，否则不具有很强的传染性。blCP0是一种病毒蛋白，可以刺激所有类别的病毒启动子的表达。基于这些和其他研究，我们假设blCP0与细胞蛋白相互作用和改变功能的能力刺激病毒转录。如果这一预测是正确的，激活病毒转录的细胞蛋白可能在一定程度上取代blCP0的功能。腺病毒E11A基因和blCP0编码的蛋白质是病毒基因表达的强大激活剂，它们不特异性地结合DNA，这两种蛋白质都与染色质重塑LIN酶相互作用。由于这些功能上的相似性，最初对Ell A进行了测试，以确定它是否可以刺激BHV-1生产性感染。Ell A持续刺激BHV-1产生性感染，但不如blCP0有效。E1a结合Rb家族成员的能力在刺激生殖性感染中起作用，提示E2F家族成员激活生殖性感染。E2F-4，而不是E2F-1，E2F-2或E2F-5，以与E11A相似的效率激活生产性感染。其次，我们检测了E2F家族成员激活BHV-1立即早期(IE)转录单位1(IEtu1)启动子的能力，因为它调节了blCP0和blCP4的IE表达。E2F-1和E2F-2可强烈激活IEtu1启动子，但不能激活BHV-1 IEtu2启动子或单纯疱疹病毒1型ICPO启动子。这些研究表明，E2F家族成员可以刺激BHV-1生产性感染。
Identifying cellular genes that promote bovine herpesvirus-1 (BHV-1) productive infection is important, as BHV-1 is a significant bovine pathogen. Previous studies demonstrated that BHV-1 DNA is not very infectious unless cotransfected with a plasmid expressing blCP0, a viral protein that stimulates expression of all classes of viral promoters. Based on these and other studies, we hypothesize that the ability of blCP0 to interact with and modify the function of cellular proteins stimulates virus transcription. If this prediction is correct, cellular proteins that activate virus transcription could, in part, substitute for blCP0 functions. The adenovirus Ell A gene and blCP0 encode proteins that are potent activators of viral gene expression, they do not specifically bind DNA and both proteins interact with chromatin-remodel ling enzymes. Because of these functional similarities, Ell A was tested initially to see if it could stimulate BHV-1 productive infection. Ell A consistently stimulates BHV-1 productive infection, but not as efficiently as blCP0. The ability of E1A to bind Rb family members plays a role in stimulating productive infection, suggesting that E2F family members activate productive infection. E2F-4, but not E2F-1, E2F-2 or E2F-5, activates productive infection with similar efficiency as Ell A. Next, E2F family members were examined for their ability to activate the BHV-1 immediate-early (IE) transcription unit 1 (IEtu1) promoter, as it regulates IE expression of blCP0 and blCP4. E2F-1 and E2F-2 strongly activate the IEtu1 promoter, but not a BHV-1 IEtu2 promoter or a herpes simplex virus type 1 ICPO promoter construct. These studies suggest that E2F family members can stimulate BHV-1 productive infection.