Cryo-EM structures of human hepatitis B and woodchuck hepatitis virus small spherical subviral particles

Haitao Liu, Xupeng Hong, Ji Xi, Stephan Menne, Jianming Hu, Joseph Che-Yen Wang

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The loss of detectable hepatitis B surface antigen (HBsAg) is considered a functional cure in chronic hepatitis B. Naturally, HBsAg can be incorporated into the virion envelope or assembled into subviral particles (SVPs) with lipid from host cells. Until now, there has been no detailed structure of HBsAg, and the published SVP structures are controversial. Here, we report the first subnanometer-resolution structures of spherical SVP from hepatitis B virus (HBV) and the related woodchuck hepatitis virus (WHV) determined by cryo-electron microscopy in combination with AlphaFold2 prediction. Both structures showed unique rhombicuboctahedral symmetry with 24 protruding spikes comprising dimer of small HBsAg with four helical domains. The lipid moiety in the SVP is organized in a noncanonical lipid patch instead of a lipid bilayer, which can accommodate the exposed hydrophobic surface and modulate particle stability. Together, these findings advance our knowledge of viral membrane organization and the structures of HBV and WHV spherical SVPs.

Original languageEnglish (US)
Article numbereabo4184
JournalScience Advances
Volume8
Issue number31
DOIs
StatePublished - Aug 2022

All Science Journal Classification (ASJC) codes

  • General

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