A群轮状病毒（RVA）是引起婴幼儿和多种幼龄动物发生严重急性胃肠炎的主要病原之一，给人类健康和畜牧业发展造成巨大危害。RVA感染首先破坏细胞骨架，突破细胞膜，引发腹泻，但细胞骨架蛋白在RVA感染中的作用并不清楚。前期开展的RVA和宿主细胞的相互作用组学研究发现，细胞骨架蛋白ADD1与RVA外壳蛋白VP4存在较强的相互作用，并且可以抑制人和猪RVA的增殖，但其作用机制尚不清楚。本项目拟进一步从体内和体外两方面系统分析ADD1在RVA增殖过程中的作用，确定其发挥作用的功能域或关键氨基酸位点，明确其抑制RVA增殖的具体环节，探讨ADD1磷酸化、调节actin以及离子转运等功能对RVA增殖的影响，解析ADD1与VP4互作的分子细节及生物学意义，揭示ADD1抑制RVA增殖的分子机制，为进一步阐明RVA的致病机制奠定基础，为研制更加安全有效的新型疫苗提供理论依据，具有重要的理论和实践意义。

Group A rotavirus (RVA) is a major cause of acute viral gastroenteritis in children and young animals worldwide, posing tremendous threats to human health and animal husbandry development. RVA infection disrupts the cytoskeleton, penetrates through the cell membrane, and induces diarrhea. However, the role of cytoskeletal proteins in RVA infection is not clear. Our previous studies of RVA-host interactions revealed that host cytoskeletal protein ADD1 potently interacts with RVA outer capsid protein VP4, and that ADD1 inhibits the proliferation of human and porcine RVAs, although the underlying mechanism remains elusive. Based on these preliminary findings, here we plan to 1) analyze the inhibitory role of ADD1 in the replication of RVA both in vivo and in vitro, 2) identify its functional antiviral domains and key amino acid sites, 3) explore how ADD1 phosphorylation, regulation of actin filaments and ion transporter affects RVA replication, 4) investigate the molecular details and biological significance of the interaction of ADD1 and VP4. Collectively our study will reveal the molecular mechanism of ADD1 inhibition of RVA replication and lay the foundation for better understanding the mechanism(s) of pathogenesis of RVA, thereby providing theoretical basis and scientific basis for developing the safe and effective new vaccine.