Bovine Herpesvirus 1 Regulatory Proteins bICP0 and VP16 Are Readily Detected in Trigeminal Ganglionic Neurons Expressing the Glucocorticoid Receptor during the Early Stages of Reactivation from Latency
Bovine Herpesvirus 1 Regulatory Proteins bICP0 and VP16 Are Readily Detected in Trigeminal Ganglionic Neurons Expressing the Glucocorticoid Receptor during the Early Stages of Reactivation from Latency
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DOI：
10.1128/jvi.01737-13
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发表时间：
2013-10-01
影响因子：
5.4
通讯作者：
Jones, Clinton
中科院分区：
文献类型：
--
作者：
da Silva, Leticia Frizzo;Kook, Insun;Jones, Clinton
牛疱疹病毒1型(BHV-1)在急性感染后在感觉神经元中建立终生潜伏感染。应激引起的皮质类固醇水平升高会增加潜伏期重新激活的几率。在几分钟内，皮质类固醇就会激活糖皮质激素受体和含有糖皮质激素受体元件的启动子的转录。单次静脉注射合成皮质类固醇地塞米松可持续诱导小牛从潜伏期重新激活。对潜伏感染BHV-1的小牛，地塞米松治疗后6h内可检测到溶解周期病毒基因的表达。地塞米松治疗后1.5h内，三叉神经节神经元中地塞米松诱导了细胞转录因子的表达，提示地塞米松在潜伏期再激活的早期阶段促进了病毒基因的表达，我们在操作上将其定义为逃避潜伏期。在这项研究中，利用免疫组织化学方法检测潜伏期逃避过程中病毒蛋白的表达。在地塞米松作用后1.5h内，三叉神经节神经元中可持续检测到bICP0和晚期蛋白VP16。大多数表达bICP0的神经元也表达VP16。进一步的研究表明，在地塞米松处理1.5h后，表达糖皮质激素受体的神经元也表达了bICP0或VP16。另外两种晚期蛋白糖蛋白C和D在地塞米松处理后6h才被检测到，并且仅在少数神经元中检测到。这些研究提供的证据表明，VP16和杂乱的病毒反式激活因子(BICP0)在潜伏期逃避期间表达，表明它们促进了潜伏期感染神经元的一小部分产生感染性病毒。
Bovine herpesvirus 1 (BHV-1) establishes a lifelong latent infection in sensory neurons following acute infection. Increased corticosteroid levels, due to stress, increases the incidence of reactivation from latency. Within minutes, corticosteroids activate the glucocorticoid receptor and transcription of promoters containing a glucocorticoid receptor element. A single intravenous injection of the synthetic corticosteroid dexamethasone consistently induces reactivation from latency in calves. Lytic cycle viral gene expression is detected within 6 h after dexamethasone treatment of calves latently infected with BHV-1. Cellular transcription factors are induced by dexamethasone in trigeminal ganglionic neurons within 1.5 h after dexamethasone treatment, suggesting they promote viral gene expression during the early phases of reactivation from latency, which we operationally defined as the escape from latency. In this study, immunohistochemistry was utilized to examine viral protein expression during the escape from latency. Within 1.5 h after dexamethasone treatment, bICP0 and a late protein (VP16) were consistently detected in a subset of trigeminal ganglionic neurons. Most neurons expressing bICP0 also expressed VP16. Additional studies revealed that neurons expressing the glucocorticoid receptor also expressed bICP0 or VP16 at 1.5 h after dexamethasone treatment. Two other late proteins, glycoprotein C and D, were not detected until 6 h after dexamethasone treatment and were detected in only a few neurons. These studies provide evidence that VP16 and the promiscuous viral trans-activator (bICP0) are expressed during the escape from latency, suggesting they promote the production of infectious virus in a small subset of latently infected neurons.