Inherent symmetry and flexibility in hepatitis B virus subviral particles

• 成果类型: Article
• 署名作者: Wang, Quan; Wang, Tao; Cao, Lin; Mu, An; Fu, Sheng; Wang, Peipei; Gao, Yan; Ji, Wenxin; Liu, Zhenyu; Du, Zhanqiang; Guddat, Luke W.; Zhang, Wenchi; Li, Shuang; Li, Xuemei; Lou, Zhiyong; Wang, Xiangxi; Hu, Zhongyu; Rao, Zihe
• 署名单位: ShanghaiTech University; Chinese Academy of Sciences; Shanghai Advanced Research Institute, CAS; Tsinghua University; Nankai University; Chinese Academy of Sciences; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; University of Queensland; National Institute of Food & Drug Control - China
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9366
• DOI: 10.1126/science.adp1453
• 发表日期: 2024-09-13
• 页码: 1217-1224
• 关键词: surface-antigen; cryoelectron microscopy; transmembrane topology; expression; infection; virions; cells

摘要

Chronic hepatitis B virus (HBV) infection poses a major global health challenge with massive morbidity and mortality. Despite a preventive vaccine, current treatments provide limited virus clearance, necessitating lifelong commitment. The HBV surface antigen (HBsAg) is crucial for diagnosis and prognosis, yet its high-resolution structure and assembly on the virus envelope remain elusive. Utilizing extensive datasets and advanced cryo-electron microscopy analysis, we present structural insights into HBsAg at a near-atomic resolution of 3.7 angstroms. HBsAg homodimers assemble into subviral particles with D-2- and D-4-like quasisymmetry, elucidating the dense-packing rules and structural adaptability of HBsAg. These findings provide insights into how HBsAg assembles into higher-order filaments and interacts with the capsid to form virions.