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Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin

Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA) that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagn...

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Published in:PloS one 2014-02, Vol.9 (2), p.e89803-e89803
Main Authors: Cho, Ki Joon, Hong, Kwang W, Kim, Se-Ho, Seok, Jong Hyeon, Kim, Sella, Lee, Ji-Hye, Saelens, Xavier, Kim, Kyung Hyun
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cited_by cdi_FETCH-LOGICAL-c692t-d63c177989be0a405ca28bed5feea1592d266a87cc3c34e6b0cb7767b81615163
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description Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA) that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagnostics. We produced and characterized nine monoclonal antibodies that showed significant neutralizing activities against H1 subtype influenza viruses, and determined the complex structure of HA derived from a 2009 pandemic virus A/Korea/01/2009 (KR01) and the Fab fragment from H1-specific monoclonal antibody GC0587. The overall structure of the complex was essentially identical to the previously determined KR01 HA-Fab0757 complex structure. Both Fab0587 and Fab0757 recognize readily accessible head regions of HA, revealing broadly shared and conserved antigenic determinants among H1 subtypes. The β-strands constituted by Ser110-Glu115 and Lys169-Lys170 form H1 epitopes with distinct conformations from those of H1 and H3 HA sites. In particular, Glu112, Glu115, Lys169, and Lys171 that are highly conserved among H1 subtype HAs have close contacts with HCDR3 and LCDR3. The differences between Fab0587 and Fab0757 complexes reside mainly in HCDR3 and LCDR3, providing distinct antigenic determinants specific for 1918 pdm influenza strain. Our results demonstrate a potential key neutralizing epitope important for H1 subtype specificity in influenza virus.
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subjects Amino acids
Antibodies, Monoclonal - immunology
Antigenic determinants
Antigens
Base Sequence
Bioinformatics
Biology
Biotechnology
Conserved Sequence - genetics
Crystallization
Crystallography
Epidemics
Epitopes
Epitopes - genetics
Hemagglutinin Glycoproteins, Influenza Virus - genetics
Hemagglutinins
Immunoglobulins
Influenza
Influenza A Virus, H1N1 Subtype - genetics
Influenza A Virus, H1N1 Subtype - immunology
Influenza viruses
Laboratories
Lectins
Medicine
Models, Molecular
Molecular Sequence Data
Monoclonal antibodies
Mutation
Neutralization Tests
Neutralizing
Pandemics
Protein Conformation
Proteins
Sequence Alignment
Swine flu
Vaccines
Viruses
title Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin
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