厦门大学夏宁邵等课题组首次解析水痘带状疱疹病毒衣壳的结构

来源：病毒学界

该研究发现VZV衣壳主要存在两种颗粒类型，分别为包含病毒核酸的成熟衣壳与不含核酸的空心衣壳。应用冷冻电镜技术与局部重构技术首次获得了两种衣壳的近原子分辨率结构，分辨率分别为4.1 Å和3.5 Å，提供精细的衣壳组成与结构特征信息。【图1】

图1 VZV A和C衣壳的Cryo-EM模型

进一步的研究发现，VZV衣壳具有更多的柔性区域，且衣壳蛋白之间、衣壳与皮层蛋白之间的相互作用均相对较弱，但VZV衣壳依然具有结构稳定性；VZV衣壳具有其感染必不可少的SCP衣壳蛋白，该结构延伸VZV病毒颗粒皮层柔性C端区域，该区域与VZV衣壳出核和包膜组装直接相关。该研究首次揭示疱疹病毒a家族VZV不同类型核衣壳结构，填补了人类疱疹病毒VZV结构信息的空白，为光谱抗病毒药物和新型疫苗研制提供理论基础。

Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome that is substantially smaller than those of other human herpesviruses, VZV has a similarly sized capsid, consisting of 955 major capsid protein (MCP), 900 small capsid protein (SCP), 640 triplex dimer (Tri2) and 320 triplex monomer (Tri1) subunits. The VZV capsid has high thermal stability, although with relatively fewer intra- and inter-capsid protein interactions and less stably associated tegument proteins compared with other human herpesviruses. Analysis with antibodies targeting the N and C termini of the VZV SCP indicates that the hexon-capping SCP—the largest among human herpesviruses—uses its N-terminal half to bridge hexon MCP subunits and possesses a C-terminal flexible half emanating from the inner rim of the upper hexon channel into the tegument layer. Correlation of these structural features and functional observations provide insights into VZV assembly and pathogenesis and should help efforts to engineer gene delivery and anticancer vectors based on the currently available VZV vaccine.