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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 |
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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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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0089803</identifier><identifier>PMID: 24587046</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2014-02, Vol.9 (2), p.e89803-e89803</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Cho et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Cho et al 2014 Cho et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-d63c177989be0a405ca28bed5feea1592d266a87cc3c34e6b0cb7767b81615163</citedby><cites>FETCH-LOGICAL-c692t-d63c177989be0a405ca28bed5feea1592d266a87cc3c34e6b0cb7767b81615163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1502642261/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1502642261?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24587046$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cho, Ki Joon</creatorcontrib><creatorcontrib>Hong, Kwang W</creatorcontrib><creatorcontrib>Kim, Se-Ho</creatorcontrib><creatorcontrib>Seok, Jong Hyeon</creatorcontrib><creatorcontrib>Kim, Sella</creatorcontrib><creatorcontrib>Lee, Ji-Hye</creatorcontrib><creatorcontrib>Saelens, Xavier</creatorcontrib><creatorcontrib>Kim, Kyung Hyun</creatorcontrib><title>Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Amino acids</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antigenic determinants</subject><subject>Antigens</subject><subject>Base Sequence</subject><subject>Bioinformatics</subject><subject>Biology</subject><subject>Biotechnology</subject><subject>Conserved Sequence - genetics</subject><subject>Crystallization</subject><subject>Crystallography</subject><subject>Epidemics</subject><subject>Epitopes</subject><subject>Epitopes - genetics</subject><subject>Hemagglutinin Glycoproteins, Influenza Virus - genetics</subject><subject>Hemagglutinins</subject><subject>Immunoglobulins</subject><subject>Influenza</subject><subject>Influenza A Virus, H1N1 Subtype - genetics</subject><subject>Influenza A Virus, H1N1 Subtype - immunology</subject><subject>Influenza viruses</subject><subject>Laboratories</subject><subject>Lectins</subject><subject>Medicine</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Monoclonal antibodies</subject><subject>Mutation</subject><subject>Neutralization Tests</subject><subject>Neutralizing</subject><subject>Pandemics</subject><subject>Protein Conformation</subject><subject>Proteins</subject><subject>Sequence Alignment</subject><subject>Swine 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into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin</title><author>Cho, Ki Joon ; Hong, Kwang W ; Kim, Se-Ho ; Seok, Jong Hyeon ; Kim, Sella ; Lee, Ji-Hye ; Saelens, Xavier ; Kim, Kyung Hyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-d63c177989be0a405ca28bed5feea1592d266a87cc3c34e6b0cb7767b81615163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Amino acids</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antigenic determinants</topic><topic>Antigens</topic><topic>Base Sequence</topic><topic>Bioinformatics</topic><topic>Biology</topic><topic>Biotechnology</topic><topic>Conserved Sequence - genetics</topic><topic>Crystallization</topic><topic>Crystallography</topic><topic>Epidemics</topic><topic>Epitopes</topic><topic>Epitopes - genetics</topic><topic>Hemagglutinin Glycoproteins, Influenza Virus - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24587046</pmid><doi>10.1371/journal.pone.0089803</doi><tpages>e89803</tpages><oa>free_for_read</oa></addata></record> |
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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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