| RRC ID |
38465
|
| 著者 |
Xing L, Wang JC, Li TC, Yasutomi Y, Lara J, Khudyakov Y, Schofield D, Emerson SU, Purcell RH, Takeda N, Miyamura T, Cheng RH.
|
| タイトル |
Spatial configuration of hepatitis E virus antigenic domain.
|
| ジャーナル |
J Virol
|
| 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.
|
| 巻・号 |
85(2)
|
| ページ |
1117-24
|
| 公開日 |
2011-1-1
|
| DOI |
10.1128/JVI.00657-10
|
| PII |
JVI.00657-10
|
| PMID |
21068233
|
| PMC |
PMC3020005
|
| MeSH |
Animals
Antibodies, Monoclonal / immunology
Antibodies, Viral / immunology
Antigens, Viral / genetics
Antigens, Viral / immunology*
Antigens, Viral / metabolism
Capsid Proteins / genetics
Capsid Proteins / immunology*
Capsid Proteins / metabolism
Cell Line
Cryoelectron Microscopy
Epitopes / immunology*
Female
Hepatitis E virus / immunology*
Image Processing, Computer-Assisted
Mice
Mice, Inbred BALB C
Models, Molecular
Protein Binding
Protein Multimerization
Sequence Deletion
Spodoptera
Virosomes / metabolism
|
| IF |
4.501
|
| 引用数 |
49
|
|
WOS 分野
|
VIROLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
