传染性法氏囊病（IBD）是禽类重要的免疫抑制病，超强毒（vvIBDV）对养鸡业危害更严重。IBDV强、弱毒遗传背景及基因组极其相似，但生物学性状完全不同。由于不十分清楚强、弱毒侵染宿主差异及其机制，防疫用疫苗毒力被不断盲目提高，虽然靠对靶细胞的暂时占位效应提供了免疫保护，但却导致严重免疫抑制和生物安全隐患。本研究以vvIBDV及其致弱株为主要研究模型，研究其基因组和功能差异及协同机制，重构病毒粒子结构，揭示IBDV遗传变异的分子及结构基础；筛选强、弱毒与体内B细胞和体外CEF细胞膜中的互作蛋白，鉴定病毒细胞受体，解析强、弱毒株细胞嗜性和入侵细胞差异的分子机制；筛选鉴定强、弱毒与宿主细胞内的互作蛋白及信号通路，解析宿主天然免疫等因素影响强、弱毒复制的分子机制。分析IBDV与宿主互作的主要网络，阐明强、弱毒侵染宿主细胞的分子机制及其差异，为传染性法氏囊病新型疫苗研发及安全合理防控提供理论依据。

Infectious bursal disease (IBD) is an important avian immunosuppressive disease. The very virulent infectious bursal disease virus (vvIBDV) threaten poultry industry more seriously. Very virulent and attenuated strains of IBDV are quite different on biological characteristics, although their genetic and genome background are very similar. Because of poorly understand of the differences and its mechanism between virulent and attenuated strains, the virulent strains were blindly used as hot vaccine for control of IBD in some fields. Although virulent strains provide temporary protection from the infection by IBDV, they induce severe immunosuppression and biosafety risks. In this project, the genome function and its coordination mechanism will be researched, and the three-dimensional structure of very virulent and attenuated IBDV will be reconstructed in order to figure out the molecular and structural basis of genetic variation and virulence enhance of vvIBDV. The host cytomembrane proteins interacted with virulent and attenuated IBDV will be screened from B cell of bursa of Fabricius and chicken embryo fibroblast cell (CEF) respectively, the cell receptors for IBDV will be identified, and the mechanism of attachment to host cell for virulent and attenuated strain will be expounded. The host intracellular proteins of B and CEF cell and the relevant signal pathway interacted with virulent and attenuated IBDV will be illuminated respectively, and the innate immunity and its mechanism involved in the replication of virulent and attenuated strain will be illustrated. Totally, the signaling network involved in the interaction between virulent and attenuated strains and host cells will be analyzed systematically, the molecular mechanism of host cells invasion of IBDV and the relevant differences between virulent and attenuated IBDV will be clarified, which will provide theoretical basis for new vaccines development and the prevention and control of IBD safely and appropriately.