传染性法氏囊病毒（IBDV）感染宿主细胞的分子基础与致病机理

鸡传染性法氏囊病（IBD）是由鸡传染性法氏囊病病毒（IBDV）引起的鸡的一种急性、高度传染性和免疫抑制性疾病。由于IBDV感染严重损伤靶器官（法氏囊），致使病鸡存活后出现严重的免疫抑制，易继发感染多种疾病。然而对IBDV如何感染宿主细胞的分子基础和致病机理还不清楚。我们在前期研究中发现，IBDVVP4与宿主细胞靶蛋白GILZ互作抑制I型干扰素的表达，而VP5作用于VDAC2引起宿主细胞凋亡。本项目在前期研究的基础上，通过研究IBDV病毒蛋白（VP1-VP5）以及相关miRNA在宿主细胞中的作用及其关键氨基酸对病毒复制和免疫应答的影响，深入解析IBDV引起细胞凋亡和免疫抑制的分子机理，揭示IBDV感染宿主细胞的分子基础和致病机理，为研制新型IBDV疫苗以及免疫防控提供理论指导，也为解析其他免疫抑制性病原的致病机理提供参考。

Infectious Bursal Disease (IBD) is an acute, highly contagious and immunosuppressive avian disease caused by IBD virus (IBDV). IBDV infection causes severe damages in Bursa of Fabricius as a target organ, leading to deep immunosuppression in hosts that become more susceptible to secondary infections. Although IBDV-induced host cell apoptosis and immunosuppression have been established, the underlying molecular mechanisms are still unclear. In our previous reports, we show that IBDV protein VP4 suppresses type I interferon expresson via interaction with host cellular target protein GILZ, while VP5 induces apoptosis in host cells via interaction with cellular protein VDAC2. Based on our previous findings, this project is designed to uncover the molecular basis and pathogenesis of IBDV infection by elucidating the roles of IBDV viral proteins (VP1-VP5) and related micro-RNAs in host cell response and the effects of critical amino acids of viral proteins on viral replication and immune response and to further analyze the molecular mechanisms underlying IBDV-induced apoptosis and immunosuppression. The findings from this study will help to provide theoretical guidance for the development of novel IBDV vaccines and for the immunological control of diseases, and will also serve as references for elucidating the pathogenesis of other immunosuppressive pathogens.