c-Src激酶-整合素α4β1分子模块在传染性法氏囊病病毒感染B淋巴细胞过程中的作用及分子机制研究

传染性法氏囊病病毒（IBDV）主要侵染雏鸡法氏囊内的未成熟B淋巴细胞，引起严重的免疫抑制，然而IBDV侵入宿主B淋巴细胞及其建立感染的分子机制尚不清楚。c-Src是一种非受体型蛋白酪氨酸激酶，参与介导整合素信号的转导过程而被激活，在病毒侵入宿主细胞过程中发挥重要功能。本项目首先从体外建立的B淋巴细胞感染模型着手，研究IBDV感染与B淋巴细胞内c-Src激酶磷酸激酶活性水平动态变化之间的关系；其次，体内实验研究IBDV强弱毒株的感染与c-Src激酶磷酸化之间的关系，明确c-Src激酶磷酸激酶活性水平与IBDV毒力的相关性；最后，进一步探讨c-Src激酶-整合素α4β1分子模块对胞内关键信号通路PI3K-Akt的调控和对细胞骨架重排的影响及其分子机制。这将为解析和阐明IBDV导致的免疫抑制机制提供新理论，并为进一步开发用于IBD防治的小分子药物提供新靶点。

Infectious bursal disease virus (IBDV), the causative agent of infectious bursal disease (IBD), mainly destroys the immature B lymphocyte resulting in severe immunosuppression. However, the mechanism by which IBDV invades and infects B cells remains elusive. c-Src kinase is a member belonging to a family of non-receptor protein tyrosine kinase, and together with adhesion molecule integrins, plays key roles in the regulation of viral strategies for evading host cells. In this study, we aim to explore the roles of c-Src-integrin α4β1 module in IBDV infection of B cells. We will investigate the c-Src kinase dynamic phosphorylation in B cells upon IBDV infection over a time course. The correlation between the c-Src kinase phosphorylation induced and the viral virulence will be established. Furthermore, the roles of c-Src kinase-integrin α4β1 module in the regulation of PI3K-Akt signaling pathway and cytoskeleton reorganization during IBDV infection will be examined. Together, these data will for the first time provide new insights into the how IBDV invades and establishes infection in B cells, and lead to the development of pharmacological interventions and clinical strategies for treatment of IBDV induced immunosuppression.