水痘-带状疱疹病毒的衣壳结构与衣壳蛋白相互作用机制研究

水痘-带状疱疹病毒（VZV）是导致水痘与带状疱疹的病原体，具有较严重的危害，目前仍缺乏针对性治疗药物。衣壳形成是病毒感染复制周期的必由步骤，也是研制抗病毒药物的良好靶标。然而，目前仍缺乏对VZV衣壳精确结构与衣壳蛋白相互作用机制的系统认识。课题组在前期工作中已建立了较成熟的VZV基础研究技术平台与病毒颗粒纯化方法，已成功初步开展了VZV衣壳颗粒的冷冻电镜（Cryo-EM）结构分析。本研究将在前期工作基础上深入开展VZV衣壳颗粒的结构与组装基础研究，应用Cryo-EM技术获得VZV不同类型衣壳颗粒的高分辨率结构，阐明衣壳颗粒的精确结构特征和分子组成，揭示VZV衣壳组成蛋白之间的相互作用网络和影响衣壳组装的关键氨基酸和结构域，初步阐释VZV衣壳组装机制。本研究结果将有助于增进对VZV感染复制机制的认识，进一步丰富和完善疱疹病毒衣壳结构与组装的基础研究理论，为发展新型的抗病毒药物提供科学支持。

Varicella-zoster virus (VZV) is the causative agent of both chickenpox and shingles, and there is still no specific drug to treat VZV-induced diseases. Viral capsid assembly is an essential step of virus infection and replication, and can be used as a good target for drug design. However, there is still a lack of understanding of the precise structure of the VZV capsid and the interaction mechanism between capsid proteins. In the previous work, our group has established sophisticated technology platform for basic research on VZV and developed efficient methods for large-scale preparation and purification of VZV capsids. Furthermore, we have successfully determined an intermediate resolution structure of the VZV capsid by cryo-electron microscopy (Cryo-EM). In this proposal, we will systematically carry out the basic research on the structure and assembly of different types of VZV capsids. We aim to obtain the high-resolution three-dimensional structure of the VZV capsid by Cryo-EM, identify the precise structure characteristics and composition of VZV capsids, and determine the protein-protein interaction network between capsid proteins and key amino acids or domains that affect capsid assembly, as well as reveal the assembly mechanism. We expect the results of this study will enhance our understanding of the VZV life cycle, further enrich and improve the understanding of the structure and assembly of herpesvirus capsid, and provide scientific support for the development of new antiviral drugs and therapies.