《生命科学》 2025, 37(7): 787-794

乙型肝炎病毒表面抗原结构研究进展

慕　安^1,2 , 王佩佩² , 王　权^2,3,*

¹中国科学院生物物理研究所，北京 100101 ²上海科技大学，上海 201210 ³中国科学院上海高等研究院国家蛋白质科学研究(上海)设施，上海 201210

摘　要：

乙型肝炎病毒(HBV) 感染是全球公共卫生的重大挑战，其表面抗原(HBsAg) 是病毒包膜的关键结构蛋白，同时也是诊断、疫苗与治疗的重要靶点。由于HBsAg 结构的高度柔性与异质性，长期以来其高分辨率三维结构一直难以获得。近年来，冷冻电镜单颗粒分析技术的发展，结合定制化的颗粒筛选与亚颗粒局部重构方法，逐步解析了HBsAg 同源二聚体以及其塑造的准对称性亚病毒颗粒(SVP) 的结构。HBsAg的近原子分辨率结构揭示了其多样寡聚体形态的结构基础和组装机制。国家蛋白质科学研究( 上海) 设施( 以下简称“蛋白质设施”) 构建的从蛋白质构象动态到原位结构、从分子到细胞尺度的综合性研究平台，不仅推动了乙肝病毒结构研究的突破，也为未来疫苗优化设计与抗病毒策略开发提供了重要条件。

通讯作者：王　权 , Email:wangq@shanghaitech.edu.cn

Recent advances in the structural studies of hepatitis B virus surface antigen

MU An^1,2 , WANG Pei-Pei² , WANG Quan^2,3,*

¹Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China ²ShanghaiTech University, Shanghai 201210, China ³National Facility for Protein Science, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China

Abstract:

Hepatitis B virus (HBV) infection remains a major global public health threat. The hepatitis B surface antigen (HBsAg), a key structural component of the viral envelope, is also a central target for diagnosis, vaccination, and antiviral therapy. Due to its intrinsic flexibility and structural heterogeneity, high-resolution three-dimensional structures of HBsAg have long been difficult to obtain. Recent advances in single-particle cryo-electron microscopy, combined with customized particle selection and subparticle local reconstruction methods, have enabled the determination of the structures of the HBsAg homodimer and its quasi-symmetric subviral particle (SVP) assemblies. These near-atomic resolution structures reveal the structural basis and assembly mechanisms underlying the diverse oligomeric forms of HBsAg. The National Facility for Protein Science (Shanghai) has provided an integrated research platform spanning dynamic conformational analysis to in situ structural studies at molecular to cellular scales, which has played a pivotal role in enabling these breakthroughs. This progress not only advances our understanding of HBV structural biology but also lays a solid foundation for rational vaccine design and the development of new antiviral strategies.

Communication Author：WANG Quan , Email:wangq@shanghaitech.edu.cn