柯萨奇病毒A10（CVA10）近年来已成为导致手足口病（HFMD）的主要病原体，但目前由CVA10引起的HFMD暂无特效药及有效的预防性疫苗。我们前期研究发现CVA10培养病毒中存在前体衣壳、中间态A颗粒和成熟颗粒三种形式的病毒粒子，且筛选出一类对三种颗粒具有交叉结合能力的优势中和抗体，但尚不了解颗粒的结构特征及该类中和抗体的表位特征和作用机制。本课题拟应用冷冻电镜三维重构技术，解析三种病毒颗粒及其与优势中和抗体复合物的高分辨率Cryo-EM结构，比较CVA10不同病毒形式的结构差异，分析优势中和表位的关键氨基酸组成和结构特征，应用系列病毒学和生化分析方法研究中和抗体与不同病毒颗粒的相互作用，初步揭示优势中和抗体的抗病毒作用机制，为开展新型CVA10疫苗和抗病毒治疗药物研究提供结构基础和理论依据。

Coxsackievirus A10 (CVA10) recently emerged as a major pathogen of hand, foot and mouth disease worldwide, and there is no cure and effective vaccine against CVA10 infection. We found that CVA10 mainly exist three predominant types of particles in infected cell: procapsids, intermediate (or A-particle) and mature virions, and obtained a class of immune-dominant neutralizing antibodies that can corss-react three types of particles. However, the structure of CVA10 particles, the characteristics of their neutralizing epitopes, and mechanisms of antibody protection remains unknown. Basing on preliminary studies, in this study, we will analysis high-resolution Cryo-EM structure of three types of particles and virus-Fab immune-complexes using three-dimensional reconstruction of cryo-electron microscopy (Cryo-EM), compare structural differences among three types, analyze the critical amino acid residues and structural characteristics of the cross-reactive and neutralizing epitope. In addition, a series of virological and biochemical analyses will provide us with clues to the antiviral mechanism of neutralizing antibodies. These knowledges can provide structural basis and theoretical guidance for studying the CVA10 vaccine and antiviral drugs.