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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Structural Insight into a Human Neutralizing Antibody against Influenza Virus H7N9</title>
<author><name sortKey="Chen, Cong" sort="Chen, Cong" uniqKey="Chen C" first="Cong" last="Chen">Cong Chen</name>
<affiliation><nlm:aff id="aff1">MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liu, Liguo" sort="Liu, Liguo" uniqKey="Liu L" first="Liguo" last="Liu">Liguo Liu</name>
<affiliation><nlm:aff id="aff1">MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Xiao, Yan" sort="Xiao, Yan" uniqKey="Xiao Y" first="Yan" last="Xiao">Yan Xiao</name>
<affiliation><nlm:aff id="aff1">MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cui, Sheng" sort="Cui, Sheng" uniqKey="Cui S" first="Sheng" last="Cui">Sheng Cui</name>
<affiliation><nlm:aff id="aff1">MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Jianmin" sort="Wang, Jianmin" uniqKey="Wang J" first="Jianmin" last="Wang">Jianmin Wang</name>
<affiliation><nlm:aff id="aff1">MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jin, Qi" sort="Jin, Qi" uniqKey="Jin Q" first="Qi" last="Jin">Qi Jin</name>
<affiliation><nlm:aff id="aff1">MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People's Republic of China</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">29212936</idno>
<idno type="pmc">5809732</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809732</idno>
<idno type="RBID">PMC:5809732</idno>
<idno type="doi">10.1128/JVI.01850-17</idno>
<date when="2018">2018</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Structural Insight into a Human Neutralizing Antibody against Influenza Virus H7N9</title>
<author><name sortKey="Chen, Cong" sort="Chen, Cong" uniqKey="Chen C" first="Cong" last="Chen">Cong Chen</name>
<affiliation><nlm:aff id="aff1">MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liu, Liguo" sort="Liu, Liguo" uniqKey="Liu L" first="Liguo" last="Liu">Liguo Liu</name>
<affiliation><nlm:aff id="aff1">MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Xiao, Yan" sort="Xiao, Yan" uniqKey="Xiao Y" first="Yan" last="Xiao">Yan Xiao</name>
<affiliation><nlm:aff id="aff1">MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cui, Sheng" sort="Cui, Sheng" uniqKey="Cui S" first="Sheng" last="Cui">Sheng Cui</name>
<affiliation><nlm:aff id="aff1">MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Jianmin" sort="Wang, Jianmin" uniqKey="Wang J" first="Jianmin" last="Wang">Jianmin Wang</name>
<affiliation><nlm:aff id="aff1">MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jin, Qi" sort="Jin, Qi" uniqKey="Jin Q" first="Qi" last="Jin">Qi Jin</name>
<affiliation><nlm:aff id="aff1">MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People's Republic of China</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint><date when="2018">2018</date>
</imprint>
</series>
</biblStruct>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>Since its first emergence in East China in early 2013, many cases of avian influenza A H7N9 have been reported. The disease has extended to 22 provinces in mainland China and some surrounding areas. Strategies to combat viral infection are urgently needed. We previously isolated a human monoclonal antibody, HNIgGA6, that neutralized the H7N9 virus both <italic>in vitro</italic>
and <italic>in vivo</italic>
. In this study, we determined the crystal structure of viral hemagglutinin (HA) globular head bound to the fragment antigen-binding region (Fab) of HNIgGA6. The crystal structure shows that the tip of the HNIgGA6 heavy-chain complementarity-determining region 3 (HCDR3) directly interposes into the receptor binding site (RBS) and mimics, in many respects, the interaction of the sialic acid receptor. Three residues at Y98, H183, and E190, which are critical to human cellular receptor binding, are also essential for HNIgGA6 recognition. Meanwhile, dual mutations at V186G and L226Q in RBS were able to disrupt viral HA1 binding with the antibody. Our study provides a better understanding of the mechanism for protective antibody recognition and a sound foundation for the design of therapeutic drugs and vaccines against H7N9 influenza.</p>
<p><bold>IMPORTANCE</bold>
Neutralization by antibody is one of the most important mechanisms for a host to defend against viral infections. Human-originated antibody HNIgGA6 was generated in response to the natural infectious H7N9 virus and showed potential for use in suppression of H7N9 infection, with possible therapeutic implications. The crystal structure of the HNIgGA6/HA1 complex provided new insight into the protective immune response to H7N9 virus in humans, as well as possibilities for the development of effective H7N9 pandemic vaccines and antiviral molecules.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Virol</journal-id>
<journal-id journal-id-type="hwp">jvi</journal-id>
<journal-id journal-id-type="pmc">jvi</journal-id>
<journal-id journal-id-type="publisher-id">JVI</journal-id>
<journal-title-group><journal-title>Journal of Virology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">29212936</article-id>
<article-id pub-id-type="pmc">5809732</article-id>
<article-id pub-id-type="publisher-id">01850-17</article-id>
<article-id pub-id-type="doi">10.1128/JVI.01850-17</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Vaccines and Antiviral Agents</subject>
</subj-group>
</article-categories>
<title-group><article-title>Structural Insight into a Human Neutralizing Antibody against Influenza Virus H7N9</article-title>
<alt-title alt-title-type="running-head">Structural Insight into an H7N9-Neutralizing Antibody</alt-title>
<alt-title alt-title-type="short-authors">Chen et al.</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Chen</surname>
<given-names>Cong</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Liguo</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Xiao</surname>
<given-names>Yan</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0001-6329-3582</contrib-id>
<name><surname>Cui</surname>
<given-names>Sheng</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Wang</surname>
<given-names>Jianmin</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Jin</surname>
<given-names>Qi</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<aff id="aff1"><label>a</label>
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China</aff>
<aff id="aff2"><label>b</label>
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People's Republic of China</aff>
</contrib-group>
<contrib-group><contrib contrib-type="editor"><name><surname>Sandri-Goldin</surname>
<given-names>Rozanne M.</given-names>
</name>
<role>Editor</role>
<aff>University of California, Irvine</aff>
</contrib>
</contrib-group>
<author-notes><corresp id="cor1">Address correspondence to Jianmin Wang, <email>jianminwang@ipbcams.ac.cn</email>
, or Qi Jin, <email>zdsys@vip.sina.com</email>
.</corresp>
<fn fn-type="other"><p><bold>Citation</bold>
Chen C, Liu L, Xiao Y, Cui S, Wang J, Jin Q. 2018. Structural insight into a human neutralizing antibody against influenza virus H7N9. J Virol 92:e01850-17. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/JVI.01850-17">https://doi.org/10.1128/JVI.01850-17</ext-link>
.</p>
</fn>
</author-notes>
<pub-date pub-type="epreprint"><day>6</day>
<month>12</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="epub"><day>12</day>
<month>2</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="collection"><day>1</day>
<month>3</month>
<year>2018</year>
</pub-date>
<volume>92</volume>
<issue>5</issue>
<elocation-id>e01850-17</elocation-id>
<history><date date-type="received"><day>24</day>
<month>10</month>
<year>2017</year>
</date>
<date date-type="accepted"><day>21</day>
<month>11</month>
<year>2017</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2018 American Society for Microbiology.</copyright-statement>
<copyright-year>2018</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
<license license-type="asm" xlink:href="https://doi.org/10.1128/ASMCopyrightv2"><license-p><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/ASMCopyrightv2">All Rights Reserved</ext-link>
.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="zjv005183319001.pdf"></self-uri>
<abstract><title>ABSTRACT</title>
<p>Since its first emergence in East China in early 2013, many cases of avian influenza A H7N9 have been reported. The disease has extended to 22 provinces in mainland China and some surrounding areas. Strategies to combat viral infection are urgently needed. We previously isolated a human monoclonal antibody, HNIgGA6, that neutralized the H7N9 virus both <italic>in vitro</italic>
and <italic>in vivo</italic>
. In this study, we determined the crystal structure of viral hemagglutinin (HA) globular head bound to the fragment antigen-binding region (Fab) of HNIgGA6. The crystal structure shows that the tip of the HNIgGA6 heavy-chain complementarity-determining region 3 (HCDR3) directly interposes into the receptor binding site (RBS) and mimics, in many respects, the interaction of the sialic acid receptor. Three residues at Y98, H183, and E190, which are critical to human cellular receptor binding, are also essential for HNIgGA6 recognition. Meanwhile, dual mutations at V186G and L226Q in RBS were able to disrupt viral HA1 binding with the antibody. Our study provides a better understanding of the mechanism for protective antibody recognition and a sound foundation for the design of therapeutic drugs and vaccines against H7N9 influenza.</p>
<p><bold>IMPORTANCE</bold>
Neutralization by antibody is one of the most important mechanisms for a host to defend against viral infections. Human-originated antibody HNIgGA6 was generated in response to the natural infectious H7N9 virus and showed potential for use in suppression of H7N9 infection, with possible therapeutic implications. The crystal structure of the HNIgGA6/HA1 complex provided new insight into the protective immune response to H7N9 virus in humans, as well as possibilities for the development of effective H7N9 pandemic vaccines and antiviral molecules.</p>
</abstract>
<kwd-group><title>KEYWORDS</title>
<kwd>H7N9</kwd>
<kwd>neutralizing antibodies</kwd>
<kwd>structural biology</kwd>
</kwd-group>
<counts><fig-count count="5"></fig-count>
<table-count count="2"></table-count>
<equation-count count="0"></equation-count>
<ref-count count="46"></ref-count>
<page-count count="12"></page-count>
<word-count count="6780"></word-count>
</counts>
<custom-meta-group><custom-meta><meta-name>cover-date</meta-name>
<meta-value>March 2018</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>
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