Productive Infection and bICP0 Early Promoter Activity of Bovine Herpesvirus 1 Are Stimulated by E2F1
Productive Infection and bICP0 Early Promoter Activity of Bovine Herpesvirus 1 Are Stimulated by E2F1
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DOI：
10.1128/jvi.00321-10
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发表时间：
2010-07-01
影响因子：
5.4
通讯作者：
Jones, Clinton
中科院分区：
文献类型：
--
作者：
Workman, Aspen;Jones, Clinton
牛疱疹病毒1型（BoHV-1）是牛的重要病毒性病原。与α疱疹病毒亚科的其他成员一样，BoHV-1在感觉神经元中建立潜伏期，并具有从潜伏期重新激活的潜力。地塞米松（DEX）治疗潜伏感染的小牛或兔子一致导致从潜伏期重新激活。编码感染细胞蛋白0（bICP 0）的BoHV-1转录物在潜伏期再激活期间始终被检测到，部分原因是bICP 0早期启动子被DEX激活。在DEX诱导的潜伏期再激活过程中，受感染的感觉神经元中细胞周期蛋白的表达受到刺激。细胞周期蛋白依赖性激酶活性磷酸化Rb（视网膜母细胞瘤肿瘤抑制基因产物）家族蛋白，并因此释放E2 F家族的转录因子，表明E2 F家族成员刺激生产性感染和/或从潜伏期再激活。在这项研究中，我们提供的证据表明，E2 F1的特定的小干扰RNA（siRNA）的抑制减少生产性感染约5倍。在瞬时转染试验中，E2 F1或E2 F2刺激bICP 0早期启动子活性至少100倍。在早期启动子内鉴定了两个E2 F响应区（ERR），一个邻近TATA盒（ERR 1），一个在TATA盒上游约600 bp处（ERR 2）。迁移率改变分析表明E2 F与ERR 1和ERR 2相互作用。E2 F1蛋白水平在感染后的后期增加，这与增强的结合到一个共识E2 F结合位点，ERR 1，或ERR 2。总的来说，这些研究表明，E2 F1刺激生产性感染和bICP 0早期启动子活性，部分原因是E2 F家族成员与ERR 1和ERR 2相互作用。
Bovine herpesvirus 1 (BoHV-1) is an important viral pathogen of cattle. Like other members of the subfamily Alphaherpesvirinae, BoHV-1 establishes latency in sensory neurons and has the potential to reactivate from latency. Dexamethasone (DEX) treatment of latently infected calves or rabbits consistently leads to reactivation from latency. The BoHV-1 transcript encoding the infected cell protein 0 (bICP0) is consistently detected during reactivation from latency, in part because the bICP0 early promoter is activated by DEX. During DEX-induced reactivation from latency, cyclin expression is stimulated in infected sensory neurons. Cyclin-dependent kinase activity phosphorylates Rb (retinoblastoma tumor suppressor gene product) family proteins and consequently releases the E2F family of transcription factors, suggesting that E2F family members stimulate productive infection and/or reactivation from latency. In this study, we provide evidence that repression of E2F1 by a specific small interfering RNA (siRNA) reduced productive infection approximately 5-fold. E2F1 or E2F2 stimulated bICP0 early promoter activity at least 100-fold in transient transfection assays. Two E2F-responsive regions (ERR) were identified within the early promoter, with one adjacent to the TATA box (ERR1) and one approximately 600 bp upstream from the TATA box (ERR2). Mobility shift assays suggested that E2F interacts with ERR1 and ERR2. E2F1 protein levels were increased at late times after infection, which correlated with enhanced binding to a consensus E2F binding site, ERR1, or ERR2. Collectively, these studies suggest that E2F1 stimulates productive infection and bICP0 early promoter activity, in part because E2F family members interact with ERR1 and ERR2.