Inherent symmetry and flexibility in hepatitis B virus subviral particles
Quan Wang, Tao Wang, Lin Cao, A. Mu, Sheng Fu, Peipei Wang, Yan Gao, Wenxin Ji, Zhenyu Liu, Zhanqiang Du, Luke W. Guddat, Wenchi Zhang, Shuang Li, Xuemei Li, Zhiyong Lou, Xiangxi Wang, Zhongyu Hu, Zihe Rao
Abstract
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.