猪圆环病毒感染细胞自噬与凋亡调控的信号传导机制

项目名称： 猪圆环病毒感染细胞自噬与凋亡调控的信号传导机制

项目编号： No.31272534

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： 方维焕

作者单位： 浙江大学

项目金额： 80万元

中文摘要： 猪圆环病毒2型（PCV2）是导致断奶仔猪多系统衰竭综合症的病原，给养猪业造成严重经济损失。PCV2可引起细胞凋亡，我们发现PCV2也可诱导细胞自噬，并以此促进其自身复制。但PCV2诱导上述细胞反应以及PCV2感染淋巴组织的病理学机制还有待深入研究。本项目拟系统研究：（1）PCV2感染和表达病毒蛋白的真核质粒转染细胞的内质网应激、自噬和凋亡及其介导的信号传导途径；（2）PCV2编码蛋白引起相关细胞反应的主要结构域；（3）构建该结构域突变的重组PCV2，感染体外培养细胞和小鼠，解析PCV2感染引起宿主细胞自噬或/和凋亡以及淋巴样组织的病理学变化的机制;（4）比较分析组织细胞中病毒复制与相关细胞反应的关系。通过解析PCV2介导细胞反应的特征和信号传导途径，解明PCV2感染引起宿主组织病变的细胞病理学基础。研究结果为深入研究PCV2的致病机制、探寻抗PCV2药物筛选的靶标奠定基础。

中文关键词： 猪圆环病毒2型；内质网应激；自噬；凋亡；

英文摘要： Porcine circovirus 2 is the causative agent of post-weaning wasting syndrome that incurs great economic loss to the pig industry. In addition to inducing apoptosis, we have also found that PCV2 explores the autophagic machinerary for enhanced replication in PK-15 cells. However, it remains largely unknown on the mechanisms of PCV2-induced lymphoid depletion in affected pigs. We plan to make systemic approaches on (i) the involvement of endoreticulum stress, autophagy or apoptosis in PCV2-infected cells and the underlying signal pathways; (ii) the major domain of the viral proteins causing such cellular response(s); (iii) the relationship of such cellular responses in cultured cells and in mice that are infected by recombinant PCV2 carrying mutations on the putative protein domain(s) as compared to the wild-type virus; and (iv) the relationship between cellular responses and virus replication. The ultimate goal is to elucidate the cytopathological basis of lymphoid tissues in PCV2-infected animals based on the cellular responses and the underlying signal pathway(s). The findings thus achieved will help better understand the pathogenesis of PCV2 infections and provide clues to targets for screening novel antiviral chemicals.

英文关键词： Porcine circovirus 2；ER stress；Autophagy；Apoptosis；