Spatial configuration of hepatitis e virus antigenic domain

Li Xing, Joseph C. Wang, Tian Cheng Li, Yasuhiro Yasutomi, James Lara, Yury Khudyakov, Darren Schofield, Suzanne U. Emerson, Robert H. Purcell, Naokazu Takeda, Tatsuo Miyamura, R. Holland Cheng

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Hepatitis E virus (HEV) is a human pathogen that causes acute hepatitis. When an HEV capsid protein containing a 52-amino-acid deletion at the C terminus and a 111-amino-acid deletion at the N terminus is expressed in insect cells, the recombinant HEV capsid protein can self-assemble into a T=1 virus-like particle (VLP) that retains the antigenicity of the native HEV virion. In this study, we used cryoelectron microscopy and image reconstruction to show that anti-HEV monoclonal antibodies bind to the protruding domain of the capsid protein at the lateral side of the spikes. Molecular docking of the HEV VLP crystal structure revealed that Fab224 covered three surface loops of the recombinant truncated second open reading frame (ORF2) protein (PORF2) at the top part of the spike. We also determined the structure of a chimeric HEV VLP and located the inserted B-cell tag, an epitope of 11 amino acids coupled to the C-terminal end of the recombinant ORF2 protein. The binding site of Fab224 appeared to be distinct from the location of the inserted B-cell tag, suggesting that the chimeric VLP could elicit immunity against both HEV and an inserted foreign epitope. Therefore, the T=1 HEV VLP is a novel delivery system for displaying foreign epitopes at the VLP surface in order to induce antibodies against both HEV and the inserted epitope.

Original languageEnglish (US)
Pages (from-to)1117-1124
Number of pages8
JournalJournal of Virology
Volume85
Issue number2
DOIs
StatePublished - Jan 2011

ASJC Scopus subject areas

  • Immunology
  • Virology

Fingerprint Dive into the research topics of 'Spatial configuration of hepatitis e virus antigenic domain'. Together they form a unique fingerprint.

  • Cite this

    Xing, L., Wang, J. C., Li, T. C., Yasutomi, Y., Lara, J., Khudyakov, Y., Schofield, D., Emerson, S. U., Purcell, R. H., Takeda, N., Miyamura, T., & Cheng, R. H. (2011). Spatial configuration of hepatitis e virus antigenic domain. Journal of Virology, 85(2), 1117-1124. https://doi.org/10.1128/JVI.00657-10