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 Citations (Scopus)

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

Fingerprint

Hepatitis E virus
Hepatitis Viruses
hepatitis
virus-like particles
Virion
viruses
Capsid Proteins
coat proteins
amino acid deletion
epitopes
Epitopes
Amino Acids
B-lymphocytes
B-Lymphocyte Epitopes
Cryoelectron Microscopy
Computer-Assisted Image Processing
crystal structure
virion
Recombinant Proteins
recombinant proteins

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Xing, L., Wang, J. C., Li, T. C., Yasutomi, Y., Lara, J., Khudyakov, Y., ... 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

Spatial configuration of hepatitis e virus antigenic domain. / Xing, Li; Wang, Joseph C.; Li, Tian Cheng; Yasutomi, Yasuhiro; Lara, James; Khudyakov, Yury; Schofield, Darren; Emerson, Suzanne U.; Purcell, Robert H.; Takeda, Naokazu; Miyamura, Tatsuo; Cheng, R. Holland.

In: Journal of Virology, Vol. 85, No. 2, 01.2011, p. 1117-1124.

Research output: Contribution to journalArticle

Xing, L, Wang, JC, Li, TC, Yasutomi, Y, Lara, J, Khudyakov, Y, Schofield, D, Emerson, SU, Purcell, RH, Takeda, N, Miyamura, T & Cheng, RH 2011, 'Spatial configuration of hepatitis e virus antigenic domain', Journal of Virology, vol. 85, no. 2, pp. 1117-1124. https://doi.org/10.1128/JVI.00657-10
Xing L, Wang JC, Li TC, Yasutomi Y, Lara J, Khudyakov Y et al. Spatial configuration of hepatitis e virus antigenic domain. Journal of Virology. 2011 Jan;85(2):1117-1124. https://doi.org/10.1128/JVI.00657-10
Xing, Li ; Wang, Joseph C. ; Li, Tian Cheng ; Yasutomi, Yasuhiro ; Lara, James ; Khudyakov, Yury ; Schofield, Darren ; Emerson, Suzanne U. ; Purcell, Robert H. ; Takeda, Naokazu ; Miyamura, Tatsuo ; Cheng, R. Holland. / Spatial configuration of hepatitis e virus antigenic domain. In: Journal of Virology. 2011 ; Vol. 85, No. 2. pp. 1117-1124.
@article{aa59473c0141426cbf17602ef347f529,
title = "Spatial configuration of hepatitis e virus antigenic domain",
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.",
author = "Li Xing and Wang, {Joseph C.} and Li, {Tian Cheng} and Yasuhiro Yasutomi and James Lara and Yury Khudyakov and Darren Schofield and Emerson, {Suzanne U.} and Purcell, {Robert H.} and Naokazu Takeda and Tatsuo Miyamura and Cheng, {R. Holland}",
year = "2011",
month = "1",
doi = "10.1128/JVI.00657-10",
language = "English (US)",
volume = "85",
pages = "1117--1124",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "2",

}

TY - JOUR

T1 - Spatial configuration of hepatitis e virus antigenic domain

AU - Xing, Li

AU - Wang, Joseph C.

AU - Li, Tian Cheng

AU - Yasutomi, Yasuhiro

AU - Lara, James

AU - Khudyakov, Yury

AU - Schofield, Darren

AU - Emerson, Suzanne U.

AU - Purcell, Robert H.

AU - Takeda, Naokazu

AU - Miyamura, Tatsuo

AU - Cheng, R. Holland

PY - 2011/1

Y1 - 2011/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=78650672792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650672792&partnerID=8YFLogxK

U2 - 10.1128/JVI.00657-10

DO - 10.1128/JVI.00657-10

M3 - Article

C2 - 21068233

AN - SCOPUS:78650672792

VL - 85

SP - 1117

EP - 1124

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 2

ER -