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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Main Authors: Ki Joon Cho, Kwang W Hong, Se-Ho Kim, Jong Hyeon Seok, Sella Kim, Ji-Hye Lee, Xavier Saelens, Kyung Hyun Kim
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3935945?pdf=render
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author Ki Joon Cho
Kwang W Hong
Se-Ho Kim
Jong Hyeon Seok
Sella Kim
Ji-Hye Lee
Xavier Saelens
Kyung Hyun Kim
author_facet Ki Joon Cho
Kwang W Hong
Se-Ho Kim
Jong Hyeon Seok
Sella Kim
Ji-Hye Lee
Xavier Saelens
Kyung Hyun Kim
author_sort Ki Joon Cho
collection DOAJ
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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spelling doaj.art-ab1e44a70fef4cc7b5fe797a8c1dd7ca2022-12-21T19:30:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8980310.1371/journal.pone.0089803Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin.Ki Joon ChoKwang W HongSe-Ho KimJong Hyeon SeokSella KimJi-Hye LeeXavier SaelensKyung Hyun KimInfluenza 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.http://europepmc.org/articles/PMC3935945?pdf=render
spellingShingle Ki Joon Cho
Kwang W Hong
Se-Ho Kim
Jong Hyeon Seok
Sella Kim
Ji-Hye Lee
Xavier Saelens
Kyung Hyun Kim
Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin.
PLoS ONE
title Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin.
title_full Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin.
title_fullStr Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin.
title_full_unstemmed Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin.
title_short Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin.
title_sort insight into highly conserved h1 subtype specific epitopes in influenza virus hemagglutinin
url http://europepmc.org/articles/PMC3935945?pdf=render
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