Garg Sonal, Ochetto Alyssa, Hu Jianming, Wang Joseph Che-Yen
Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA 17033, USA.
Viruses. 2024 Dec 31;17(1):48. doi: 10.3390/v17010048.
Since the discovery of the Australia antigen, now known as the hepatitis B surface antigen (HBsAg), significant research has been conducted to elucidate its physical, chemical, structural, and functional properties. Subviral particles (SVPs) containing HBsAg are highly immunogenic, non-infectious entities that have not only revolutionized vaccine development but also provided critical insights into HBV immune evasion and viral assembly. Recent advances in cryo-electron microscopy (cryo-EM) have uncovered the heterogeneity and dynamic nature of spherical HBV SVPs, emphasizing the essential role of lipid-protein interactions in maintaining particle stability. In this review, recent progress in understanding the molecular architecture of HBV SVPs is consolidated, focusing on their symmetry, lipid organization, and disassembly-reassembly dynamics. High-resolution structural models reveal unique lipid arrangements that stabilize hydrophobic residues, preserve antigenicity, and contribute to SVP functionality. These findings highlight the significance of hydrophobic interactions and lipid-protein dynamics in HBV SVP assembly and stability, offering valuable perspectives for optimizing SVP-based vaccine platforms and therapeutic strategies.
自发现澳大利亚抗原（现称为乙肝表面抗原，HBsAg）以来，人们开展了大量研究以阐明其物理、化学、结构和功能特性。含有HBsAg的亚病毒颗粒（SVPs）是高度免疫原性的非感染性实体，不仅彻底改变了疫苗研发，还为深入了解乙肝病毒免疫逃逸和病毒组装提供了关键见解。冷冻电子显微镜（cryo-EM）的最新进展揭示了球形乙肝病毒SVPs的异质性和动态性质，强调了脂蛋白相互作用在维持颗粒稳定性中的重要作用。在这篇综述中，我们总结了在理解乙肝病毒SVPs分子结构方面的最新进展，重点关注其对称性、脂质组织以及拆解-重新组装动力学。高分辨率结构模型揭示了独特的脂质排列，这些排列稳定了疏水残基、保留了抗原性并有助于SVP功能。这些发现突出了疏水相互作用和脂蛋白动力学在乙肝病毒SVP组装和稳定性中的重要性，为优化基于SVP的疫苗平台和治疗策略提供了有价值的观点。
