Varicella-zoster virus (VZV), a member of the Alphaherpesvirinae subfamily, causes severe diseases in humans of all ages. The viral capsids play critical roles in herpesvirus infection, making them potential antiviral targets. Here, we present the 3.7-Å-resolution structure of the VZV A-capsid and define the molecular determinants underpinning the assembly of this complicated viral machinery. Overall, the VZV capsid has a similar architecture to that of other known herpesviruses. The major capsid protein (MCP) assembles into pentons and hexons, forming extensive intra- and inter-capsomer interaction networks that are further secured by the small capsid protein (SCP) and the heterotriplex. The structure reveals a pocket beneath the floor of MCP that could potentially be targeted by antiviral inhibitors. In addition, we identified two alphaherpesvirus-specific structural features in SCP and Tri1 proteins. These observations highlight the divergence of different herpesviruses and provide an important basis for developing antiviral drugs.

水痘-带状疱疹病毒 (VZV)，Alphaherpesvirinae的成员亚科，会导致所有年龄段的人类发生严重疾病。病毒衣壳在疱疹病毒感染中起着关键作用，使它们成为潜在的抗病毒靶标。在这里，我们展示了 VZV A 衣壳的 3.7 Å 分辨率结构，并定义了支撑这种复杂病毒机制组装的分子决定因素。总体而言，VZV 衣壳具有与其他已知疱疹病毒相似的结构。主要衣壳蛋白 (MCP) 组装成五邻体和六邻体，形成广泛的衣壳内和衣壳间相互作用网络，并由小衣壳蛋白 (SCP) 和异源三链体进一步保护。该结构揭示了 MCP 底部下方的一个口袋，可能成为抗病毒抑制剂的目标。此外，我们在 SCP 和 Tri1 蛋白中确定了两个特定于 alphaherpesvirus 的结构特征。