Insights into varicella-zoster virus assembly from the B- and C-capsid at near-atomic resolution structures

hLife Pub Date : 2024-02-01 DOI:10.1016/j.hlife.2023.10.007
Lei Cao , Nan Wang , Zhe Lv , Wenyuan Chen , Zhonghao Chen , Lifei Song , Xueyan Sha , Guiqiang Wang , Yaling Hu , Xiaojun Lian , Guoliang Cui , Jinyan Fan , Yaru Quan , Hongrong Liu , Hai Hou , Xiangxi Wang
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Abstract

Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route. About one quarter of people are infected with this virus. Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry. In this study, we have determined the more precise detailed structures of the varicella-zoster virus (VZV) B- and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies. In addition, we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry. The structures unveil the basis for the high thermal stability of the VZV capsid. The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle. The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.

Abstract Image

从近原子分辨率结构的 B 型和 C 型囊壳透视水痘-带状疱疹病毒的组装过程
水痘-带状疱疹是一种可通过空气传播的高度传染性病毒。大约四分之一的人会感染这种病毒。以往的研究描述了 A 型囊壳的结构,以及具有二十面体对称性的 C 型囊壳的模糊重建结构。在本研究中,我们采用基于块的重建和对称松弛策略相结合的方法,确定了水痘-带状疱疹病毒(VZV)二十面体对称的 B-capsid 和 C-capsid 的更精确的详细结构。此外,我们还报告了五重对称的门户顶点重建和十二重对称的门户重建的结构细节。这些结构揭示了 VZV 荚膜具有高热稳定性的基础。噬菌体结构元素的构象灵活性在噬菌体的组装过程中发挥了作用,并推动了对病毒生命周期至关重要的过程。研究结果为开发针对这种高流行性和传染性病原体的药物开辟了新途径。
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