Insight into Highly Conserved H1 Subtype-Specific Epitopes in Influenza Virus Hemagglutinin
Identifieur interne : 000703 ( Main/Exploration ); précédent : 000702; suivant : 000704Insight into Highly Conserved H1 Subtype-Specific Epitopes in Influenza Virus Hemagglutinin
Auteurs : Ki Joon Cho [Corée du Sud] ; Kwang W. Hong [Corée du Sud] ; Se-Ho Kim [Corée du Sud] ; Jong Hyeon Seok [Corée du Sud] ; Sella Kim [Corée du Sud] ; Ji-Hye Lee [Corée du Sud] ; Xavier Saelens [Belgique] ; Kyung Hyun Kim [Corée du Sud]Source :
- PLoS ONE [ 1932-6203 ] ; 2014.
Abstract
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.
Url:
DOI: 10.1371/journal.pone.0089803
PubMed: 24587046
PubMed Central: 3935945
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Insight into Highly Conserved H1 Subtype-Specific Epitopes in Influenza Virus Hemagglutinin</title><author><name sortKey="Cho, Ki Joon" sort="Cho, Ki Joon" uniqKey="Cho K" first="Ki Joon" last="Cho">Ki Joon Cho</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Biotechnology & Bioinformatics, Korea University, Sejong, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biotechnology & Bioinformatics, Korea University, Sejong</wicri:regionArea><wicri:noRegion>Sejong</wicri:noRegion></affiliation></author><author><name sortKey="Hong, Kwang W" sort="Hong, Kwang W" uniqKey="Hong K" first="Kwang W." last="Hong">Kwang W. 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type="wicri:Area/Main/Exploration">000703</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Insight into Highly Conserved H1 Subtype-Specific Epitopes in Influenza Virus Hemagglutinin</title><author><name sortKey="Cho, Ki Joon" sort="Cho, Ki Joon" uniqKey="Cho K" first="Ki Joon" last="Cho">Ki Joon Cho</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Biotechnology & Bioinformatics, Korea University, Sejong, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biotechnology & Bioinformatics, Korea University, Sejong</wicri:regionArea><wicri:noRegion>Sejong</wicri:noRegion></affiliation></author><author><name sortKey="Hong, Kwang W" sort="Hong, Kwang W" uniqKey="Hong K" first="Kwang W." last="Hong">Kwang W. Hong</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Antibody Engineering Laboratory, Central Research Center, Green Cross Corp., Yongin Kyunggi, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Antibody Engineering Laboratory, Central Research Center, Green Cross Corp., Yongin Kyunggi</wicri:regionArea><wicri:noRegion>Yongin Kyunggi</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Se Ho" sort="Kim, Se Ho" uniqKey="Kim S" first="Se-Ho" last="Kim">Se-Ho Kim</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Antibody Engineering Laboratory, Central Research Center, Green Cross Corp., Yongin Kyunggi, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Antibody Engineering Laboratory, Central Research Center, Green Cross Corp., Yongin Kyunggi</wicri:regionArea><wicri:noRegion>Yongin Kyunggi</wicri:noRegion></affiliation></author><author><name sortKey="Seok, Jong Hyeon" sort="Seok, Jong Hyeon" uniqKey="Seok J" first="Jong Hyeon" last="Seok">Jong Hyeon Seok</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Biotechnology & Bioinformatics, Korea University, Sejong, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biotechnology & Bioinformatics, Korea University, Sejong</wicri:regionArea><wicri:noRegion>Sejong</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Sella" sort="Kim, Sella" uniqKey="Kim S" first="Sella" last="Kim">Sella Kim</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Biotechnology & Bioinformatics, Korea University, Sejong, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biotechnology & Bioinformatics, Korea University, Sejong</wicri:regionArea><wicri:noRegion>Sejong</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Ji Hye" sort="Lee, Ji Hye" uniqKey="Lee J" first="Ji-Hye" last="Lee">Ji-Hye Lee</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Biotechnology & Bioinformatics, Korea University, Sejong, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biotechnology & Bioinformatics, Korea University, Sejong</wicri:regionArea><wicri:noRegion>Sejong</wicri:noRegion></affiliation></author><author><name sortKey="Saelens, Xavier" sort="Saelens, Xavier" uniqKey="Saelens X" first="Xavier" last="Saelens">Xavier Saelens</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>VIB Inflammation Research Center, Ghent, Belgium</addr-line></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>VIB Inflammation Research Center, Ghent</wicri:regionArea><wicri:noRegion>Ghent</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium</addr-line></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Department of Biomedical Molecular Biology, Ghent University, Ghent</wicri:regionArea><orgName type="university">Université de Gand</orgName><placeName><settlement type="city">Gand</settlement><region>Région flamande</region><region type="district" nuts="2">Province de Flandre-Orientale</region></placeName></affiliation></author><author><name sortKey="Kim, Kyung Hyun" sort="Kim, Kyung Hyun" uniqKey="Kim K" first="Kyung Hyun" last="Kim">Kyung Hyun Kim</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Biotechnology & Bioinformatics, Korea University, Sejong, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biotechnology & Bioinformatics, Korea University, Sejong</wicri:regionArea><wicri:noRegion>Sejong</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kwong, Jc" uniqKey="Kwong J">JC Kwong</name></author><author><name sortKey="Stukel, Ta" uniqKey="Stukel T">TA Stukel</name></author><author><name sortKey="Lim, J" uniqKey="Lim J">J Lim</name></author><author><name sortKey="Mcgeer, Aj" uniqKey="Mcgeer A">AJ McGeer</name></author><author><name sortKey="Upshur, Re" uniqKey="Upshur R">RE Upshur</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dushoff, J" uniqKey="Dushoff J">J Dushoff</name></author><author><name sortKey="Plotkin, Jb" uniqKey="Plotkin J">JB Plotkin</name></author><author><name sortKey="Viboud, C" uniqKey="Viboud C">C Viboud</name></author><author><name sortKey="Earn, Dj" uniqKey="Earn D">DJ Earn</name></author><author><name sortKey="Simonsen, L" uniqKey="Simonsen L">L 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uniqKey="Bhardwaj A">A Bhardwaj</name></author><author><name sortKey="Walker Kopp, N" uniqKey="Walker Kopp N">N Walker-Kopp</name></author><author><name sortKey="Wilkens, S" uniqKey="Wilkens S">S Wilkens</name></author><author><name sortKey="Cingolani, G" uniqKey="Cingolani G">G Cingolani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Otwinowski, Z" uniqKey="Otwinowski Z">Z Otwinowski</name></author><author><name sortKey="Minor, W" uniqKey="Minor W">W Minor</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Adams, Pd" uniqKey="Adams P">PD Adams</name></author><author><name sortKey="Afonine, Pv" uniqKey="Afonine P">PV Afonine</name></author><author><name sortKey="Bunkoczi, G" uniqKey="Bunkoczi G">G Bunkoczi</name></author><author><name sortKey="Chen, Vb" uniqKey="Chen V">VB Chen</name></author><author><name sortKey="Davis, Iw" uniqKey="Davis I">IW Davis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emsley, P" uniqKey="Emsley P">P Emsley</name></author><author><name sortKey="Cowtan, K" uniqKey="Cowtan K">K Cowtan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brunger, At" uniqKey="Brunger A">AT Brunger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Laskowski, Ra" uniqKey="Laskowski R">RA Laskowski</name></author><author><name sortKey="Moss, Ds" uniqKey="Moss D">DS Moss</name></author><author><name sortKey="Thornton, Jm" uniqKey="Thornton J">JM Thornton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Laskowski, Ra" uniqKey="Laskowski R">RA Laskowski</name></author><author><name sortKey="Macarthus, Mw" uniqKey="Macarthus M">MW MacArthus</name></author><author><name sortKey="Moss, Ds" uniqKey="Moss D">DS Moss</name></author><author><name sortKey="Thornton, Jm" uniqKey="Thornton J">JM Thornton</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Belgique</li><li>Corée du Sud</li></country><region><li>Province de Flandre-Orientale</li><li>Région flamande</li></region><settlement><li>Gand</li></settlement><orgName><li>Université de Gand</li></orgName></list><tree><country name="Corée du Sud"><noRegion><name sortKey="Cho, Ki Joon" sort="Cho, Ki Joon" uniqKey="Cho K" first="Ki Joon" last="Cho">Ki Joon Cho</name></noRegion><name sortKey="Hong, Kwang W" sort="Hong, Kwang W" uniqKey="Hong K" first="Kwang W." last="Hong">Kwang W. Hong</name><name sortKey="Kim, Kyung Hyun" sort="Kim, Kyung Hyun" uniqKey="Kim K" first="Kyung Hyun" last="Kim">Kyung Hyun Kim</name><name sortKey="Kim, Se Ho" sort="Kim, Se Ho" uniqKey="Kim S" first="Se-Ho" last="Kim">Se-Ho Kim</name><name sortKey="Kim, Sella" sort="Kim, Sella" uniqKey="Kim S" first="Sella" last="Kim">Sella Kim</name><name sortKey="Lee, Ji Hye" sort="Lee, Ji Hye" uniqKey="Lee J" first="Ji-Hye" last="Lee">Ji-Hye Lee</name><name sortKey="Seok, Jong Hyeon" sort="Seok, Jong Hyeon" uniqKey="Seok J" first="Jong Hyeon" last="Seok">Jong Hyeon Seok</name></country><country name="Belgique"><noRegion><name sortKey="Saelens, Xavier" sort="Saelens, Xavier" uniqKey="Saelens X" first="Xavier" last="Saelens">Xavier Saelens</name></noRegion><name sortKey="Saelens, Xavier" sort="Saelens, Xavier" uniqKey="Saelens X" first="Xavier" last="Saelens">Xavier Saelens</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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