Ren Ke, Lv Yuanzi, Zhuo Yujie, Chen Changmai, Shi Hengfei, Guo Lin, Yang Guang, Hou Yayi, Tan Ren Xiang, Li Erguang
Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
College of Life Sciences, Nanjing University, Nanjing, China.
J Virol. 2016 Jul 27;90(16):7313-7322. doi: 10.1128/JVI.00563-16. Print 2016 Aug 15.
Respiratory syncytial virus (RSV) infection is a common cause of lower respiratory tract illness in infants and children. RSV is a negative-sense, single-strand RNA (ssRNA) virus that mainly infects airway epithelial cells. Accumulating evidence indicates that reactive oxygen species (ROS) production is a major factor for pulmonary inflammation and tissue damage of RSV disease. We investigated immune-responsive gene-1 (IRG1) expression during RSV infection, since IRG1 has been shown to mediate innate immune response to intracellular bacterial pathogens by modulating ROS and itaconic acid production. We found that RSV infection induced IRG1 expression in human A549 cells and in the lung tissues of RSV-infected mice. RSV infection or IRG1 overexpression promoted ROS production. Accordingly, knockdown of IRG1 induction blocked RSV-induced ROS production and proinflammatory cytokine gene expression. Finally, we showed that suppression of IRG1 induction reduced immune cell infiltration and prevented lung injury in RSV-infected mice. These results therefore link IRG1 induction to ROS production and immune lung injury after RSV infection.
RSV infection is among the most common causes of childhood diseases. Recent studies identify ROS production as a factor contributing to RSV disease. We investigated the cause of ROS production and identified IRG1 as a critical factor linking ROS production to immune lung injury after RSV infection. We found that IRG1 was induced in A549 alveolar epithelial cells and in mouse lungs after RSV infection. Importantly, suppression of IRG1 induction reduced inflammatory cell infiltration and lung injury in mice. This study links IRG1 induction to oxidative damage and RSV disease. It also uncovers a potential therapeutic target in reducing RSV-caused lung injury.
呼吸道合胞病毒（RSV）感染是婴幼儿下呼吸道疾病的常见病因。RSV是一种负链单链RNA（ssRNA）病毒，主要感染气道上皮细胞。越来越多的证据表明，活性氧（ROS）的产生是RSV疾病肺部炎症和组织损伤的主要因素。我们研究了RSV感染期间免疫反应基因1（IRG1）的表达，因为IRG1已被证明可通过调节ROS和衣康酸的产生来介导对细胞内细菌病原体的固有免疫反应。我们发现RSV感染可诱导人A549细胞和RSV感染小鼠的肺组织中IRG1的表达。RSV感染或IRG1过表达可促进ROS的产生。相应地，敲低IRG1的诱导可阻断RSV诱导的ROS产生和促炎细胞因子基因的表达。最后，我们表明抑制IRG1的诱导可减少免疫细胞浸润并预防RSV感染小鼠的肺损伤。因此，这些结果将IRG1的诱导与RSV感染后的ROS产生和免疫性肺损伤联系起来。
RSV感染是儿童疾病最常见的病因之一。最近的研究确定ROS的产生是导致RSV疾病的一个因素。我们研究了ROS产生的原因，并确定IRG1是RSV感染后将ROS产生与免疫性肺损伤联系起来的关键因素。我们发现RSV感染后A549肺泡上皮细胞和小鼠肺中IRG1被诱导。重要的是，抑制IRG1的诱导可减少小鼠的炎症细胞浸润和肺损伤。这项研究将IRG1的诱导与氧化损伤和RSV疾病联系起来。它还揭示了一个减少RSV引起的肺损伤的潜在治疗靶点。
