源自 HBV 携带者的天然球形亚病毒颗粒的冷冻电镜结构。

Cryo-EM structure of native spherical subviral particles isolated from HBV carriers.

机构信息

Institute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, 1023 South Shatai Road, Guangzhou, 510515, China; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing, 100101, China.

Department of Liver Disease, Guangdong Hospital of Traditional Chinese Medicine (Zhuhai), 53 Jingle Road, Zhuhai, 519015, China; Department of TCM, Shenzhen Hospital of Southern Medical University, 1333 Xinhu Road, Shenzhen, 518101, China.

出版信息

Virus Res. 2019 Jan 2;259:90-96. doi: 10.1016/j.virusres.2018.10.015. Epub 2018 Nov 12.

DOI:10.1016/j.virusres.2018.10.015

PMID:30391399

Abstract

Hepatitis B virus (HBV) contains 3 types of particles, i.e., 22-nm-diameter spherical and tubular subviral particles (SVPs) and 44-nm-diameter Dane particles. The SVPs are non-infectious and present strong immunogenicity, while Dane particles are infectious. In this study, we isolated spherical SVPs from HBV carriers' sera and determined their 3D structure at the resolution of ∼30 Å by cryo-electron microscopy (cryo-EM) single-particle reconstruction. Our cryo-EM structure suggests that the native HBV spherical SVP is irregularly organized, where spike-like features are arranged in a crystalline-like pattern on the surface. Strikingly, the hepatitis B surface antigen (HBsAg) in the native spherical SVPs folds as protrusions on the surface, as those on the native tubular SVPs and Dane particles, but is largely different from that in the recombinant octahedral SVPs. These results suggest a universal folding shape of HBsAg on the native HBV viral and subviral particles.

摘要

乙型肝炎病毒 (HBV) 包含 3 种类型的颗粒，即 22nm 直径的球形和管状亚病毒颗粒 (SVPs) 和 44nm 直径的 Dane 颗粒。SVPs 是非传染性的，具有很强的免疫原性，而 Dane 颗粒是传染性的。在这项研究中，我们从 HBV 携带者的血清中分离出球形 SVPs，并通过冷冻电镜 (cryo-EM) 单颗粒重建技术以约 30Å 的分辨率确定了它们的 3D 结构。我们的 cryo-EM 结构表明，天然 HBV 球形 SVP 是不规则组织的，表面上的刺状特征以结晶样图案排列。引人注目的是，天然球形 SVPs 中的乙型肝炎表面抗原 (HBsAg) 折叠成表面突起，与天然管状 SVPs 和 Dane 颗粒中的突起相似，但与重组八面体 SVPs 中的突起有很大不同。这些结果表明 HBsAg 在天然 HBV 病毒和亚病毒颗粒上具有普遍的折叠形状。