A型流感病毒激活肥大细胞的分子机制研究

项目名称： A型流感病毒激活肥大细胞的分子机制研究

项目编号： No.31272531

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 农业科学

项目作者： 胡艳欣

作者单位： 中国农业大学

项目金额： 81万元

中文摘要： 过度炎症反应致肺损伤是A型流感病毒（IAV）感染造成机体死亡的主要原因之一，但病毒感染致过度炎症反应的机制尚不明确。申请人最新研究表发现（2012，J Virol），肥大细胞(MC)的活化及其炎性介质的释放参与了IAV感染致小鼠肺损伤的过程，且MC活化被抑制后，肺损伤显著减轻，但IAV如何激活MC尚不清楚。我们推测，IAV可能首先通过唾液酸受体与MC结合进入细胞内，再通过TLR-3/RIG-1分子通路将MC激活。本研究通过解析MC表面唾液酸受体表达，揭示IAV进入MC的分子通路；接着进一步研究IAV感染MC过程中TLR3/RIG-1的表达及其通路的激活，揭示IAV激活MC的分子机制；再通过体外TALEN靶向基因敲除细胞和体内基因敲除小鼠验证TLR3/RIG-1通路在IAV激活MC过程中的作用。本研究将为明确流感病毒感染导致过度炎症反应的机制提供有价值的资料，同时可为流感的治疗提供新思路。

中文关键词： A型流感病毒；肥大细胞；Toll样受体3；细胞凋亡；

英文摘要： Diffuse alveolar damage and hemorrhage in the lungs caused by over-reactive inflammatory responses in IAV-infected animals are the major causes of mortality. And the mechanisms of inflammatory injury induced by IAV infection are still debated. Our previous study demonstrated that mast cell may play a critical role in influenza A virus infection by releasing various kinds of inflammatory molecules. Inhibiting the mast cells from activating would contribute to decreased lung injury. But the mechanism of influenza A virus activating mast cells are unknown. We hypotheses that the influenza A virus HA protein binded to sialic acid-containing cell surface receptor for virus entry. And TLR3/RIG-1 pathways were involved in the mast cell activated by virus infection. Thus, we detected the expression of sialic acid-containing cell surface receptor. Then the Study of TLR3/RIG-I knock-out mice and TLR3/RIG-I knock off cell models would reveal the role of TLR3 and RIG-I pathways in mast cell activated by influenza A virus infection. These results could provide notonly many valuable information for the mechanism of the lungs caused by over-reactive inflammatory responses during influenza infection, but also new ideas for controlling influenza infection.

英文关键词： influenza A virus；mast cells；TLR3；apoptosis；