Zhu Liqian, Thompson Jesse, Ma Fangrui, Eudy James, Jones Clinton
Oklahoma State University, Center for Veterinary Health Sciences, Department of Veterinary Pathobiology, Stillwater, OK 74078, USA; College of Veterinary Medicine and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, 48 Wenhui East Road, Yangzhou 225009, China.
University of Nebraska, Nebraska Center for Virology, Morisson Life Science Center, Lincoln, NE 68583-09065, USA.
Virology. 2017 May;505:71-79. doi: 10.1016/j.virol.2017.02.012. Epub 2017 Feb 23.
Sensory neurons are a primary site for life-long latency of bovine herpesvirus 1 (BoHV-1). The synthetic corticosteroid dexamethasone induces reactivation from latency and productive infection, in part because the BoHV-1 genome contains more than 100 glucocorticoid receptor (GR) responsive elements (GREs). Two GREs in the immediate early transcription unit 1 promoter are required for dexamethasone induction. Recent studies also demonstrated that the serum and glucocorticoid receptor protein kinase (SGK) family stimulated BoHV-1 replication. Consequently, we hypothesized that dexamethasone influences several aspects of productive infection. In this study, we demonstrated that dexamethasone increased expression of the immediate early protein bICP4, certain late transcripts, and UL23 (thymidine kinase) by four hours after infection. SGK1 expression and Akt phosphorylation were also stimulated during early stages of infection and dexamethasone treatment further increased this effect. These studies suggest that stress, as mimicked by dexamethasone treatment, has the potential to stimulate productive infection by multiple pathways.
感觉神经元是牛疱疹病毒1型（BoHV-1）终身潜伏的主要位点。合成皮质类固醇地塞米松可诱导潜伏病毒重新激活并引发增殖性感染，部分原因是BoHV-1基因组含有100多个糖皮质激素受体（GR）反应元件（GREs）。地塞米松诱导需要立即早期转录单元1启动子中的两个GREs。最近的研究还表明，血清和糖皮质激素受体蛋白激酶（SGK）家族可刺激BoHV-1复制。因此，我们推测地塞米松会影响增殖性感染的多个方面。在本研究中，我们证明地塞米松在感染后4小时增加了立即早期蛋白bICP4、某些晚期转录本和UL23（胸苷激酶）的表达。在感染早期阶段，SGK1表达和Akt磷酸化也受到刺激，地塞米松处理进一步增强了这种效应。这些研究表明，地塞米松处理模拟的应激有可能通过多种途径刺激增殖性感染。
