Inducible translational regulation of the NF-IL6 transcription factor by respiratory syncytial virus infection in pulmonary epithelial cells
Inducible translational regulation of the NF-IL6 transcription factor by respiratory syncytial virus infection in pulmonary epithelial cells
复制标题
DOI：
10.1128/jvi.70.3.1554-1563.1996
复制
发表时间：
1996-03-01
影响因子：
5.4
通讯作者：
Brasier, AR
中科院分区：
文献类型：
--
作者：
Jamaluddin, M;Garofalo, R;Brasier, AR
呼吸道合胞病毒（Respiratory syncytial virus，RSV）是小儿呼吸道疾病最常见的病原体，在人气道上皮细胞中感染和复制，导致细胞基因产物的诱导，这些基因产物是免疫和炎症反应所必需的。我们描述了RSV感染对核因子-IL 6（NF-IL 6）表达的影响，NF-IL 6是一种含亮氨酸拉链的人类碱性结构域转录因子，单独或与其他诱导型转录因子联合调节细胞因子和粘附分子基因的表达。RSV感染的人II型肺泡上皮细胞（A549）以时间依赖性方式快速合成单个45.7-kDa亚型的NF-IL 6。NF-IL 6在感染3小时后首次可检测到，并继续积累直到48小时（直到细胞失去活力）。NF-IL 6的产生不能被UV灭活的病毒诱导，证明了NF-IM合成需要病毒复制。[S-35]蛋氨酸代谢标记后进行免疫沉淀以研究NF-IL 6产生的机制。在RSV感染的（24小时）细胞内存在稳健的NF-1 L 6蛋白合成。蛋白合成发生而单个1.8-kb NF-1 L 6 mRNA的丰度或大小没有可检测的变化，由野生型或突变的NF-1 L 6结合位点驱动的转染的氯霉素乙酰转移酶报告基因的RNA酶保护测定显示NF-1 L 6依赖性转录的病毒诱导的增加，这些研究已经证明了NF-IL 6合成的翻译控制的新的诱导机制，并且鉴定了该转录因子作为宿主对RSV感染的应答的潜在效应子。
Respiratory syncytial virus (RSV), the most common etiologic agent of epidemic pediatric respiratory disease, infects and replicates in the human airway epithelium, resulting in the induction of cellular gene products essential for immune and inflammatory responses. We describe the effect of RSV infection on nuclear factor-IL6 (NF-IL6) expression, a human basic domain-leucine zipper-containing transcription factor that alone and in combination with other inducible transcription factors regulates the expression of cytokine and adhesion molecule genes. RSV-infected human type II pulmonary alveolar epithelial cells (A549) synthesize a single 45.7-kDa isoform of NF-IL6 rapidly and in a time-dependent manner. NF-IL6 is first detectable after 3 h of infection and continues to accumulate until 48 h (until the cells lose viability). NF-IL6 production could not be induced by UV-inactivated virus, demonstrating the requirement of viral replication for NF-IM synthesis. Immunoprecipitation after [S-35]methionine metabolic labeling was done to investigate the mechanism for NF-IL6 production. There was robust NF-IL6 protein synthesis within RSV-infected (24 h) cells, Protein synthesis occurred without detectable changes in the abundance or size of the single 1.8-kb NF-IL6 mRNA, RNase protection assay of transfected chloramphenicol acetyltransferase reporter genes driven by either wild-type or mutated NF-IL6 binding sites show a virus-induced increase in NF-IL6-dependent transcription, These studies have demonstrated a novel inducible mechanism for translational control of NF-IL6 synthesis and identify this transcription factor as a potential effector of the host response to RSV infection.