Recurring and Adaptable Binding Motifs in Broadly Neutralizing Antibodies to Influenza Virus Are Encoded on the D3-9 Segment of the Ig Gene
Identifieur interne : 000F24 ( Ncbi/Merge ); précédent : 000F23; suivant : 000F25Recurring and Adaptable Binding Motifs in Broadly Neutralizing Antibodies to Influenza Virus Are Encoded on the D3-9 Segment of the Ig Gene
Auteurs : Nicholas C. Wu [États-Unis] ; Seiya Yamayoshi [Japon] ; Mutsumi Ito [Japon] ; Ryuta Uraki [Japon] ; Yoshihiro Kawaoka [Japon, États-Unis] ; Ian A. Wilson [États-Unis]Source :
- Cell Host & Microbe [ 1931-3128 ] ; 2018.
Abstract
Discovery and characterization of broadly neutralizing antibodies (bnAbs) to the influenza hemagglutinin (HA) stem have provided insights for the development of a universal flu vaccine. Identification of signature features common to bnAbs from different individuals will be key to guiding immunogen design. S9-3-37 is a bnAb isolated from a healthy H5N1 vaccinee. Here, structural characterization reveals that the D3-9 gene segment of S9-3-37 contributes most of the interaction surface with the highly conserved stem epitope on HA. Comparison with other influenza bnAb crystal structures indicates that the D3-9 segment provides a general mechanism for targeting HA stem. Interestingly, such bnAbs can approach the HA stem with vastly different angles and orientations. Moreover, D3-9 can be translated in different reading frames in different bnAbs yet still target the same HA stem pocket. Thus, the D3-9 gene segment in the human immune repertoire can provide a robust defense against influenza virus.
Url:
DOI: 10.1016/j.chom.2018.09.010
PubMed: 30308159
PubMed Central: 6327842
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<front><div type="abstract" xml:lang="en"><title>Summary</title>
<p>Discovery and characterization of broadly neutralizing antibodies (bnAbs) to the influenza hemagglutinin (HA) stem have provided insights for the development of a universal flu vaccine. Identification of signature features common to bnAbs from different individuals will be key to guiding immunogen design. S9-3-37 is a bnAb isolated from a healthy H5N1 vaccinee. Here, structural characterization reveals that the D3-9 gene segment of S9-3-37 contributes most of the interaction surface with the highly conserved stem epitope on HA. Comparison with other influenza bnAb crystal structures indicates that the D3-9 segment provides a general mechanism for targeting HA stem. Interestingly, such bnAbs can approach the HA stem with vastly different angles and orientations. Moreover, D3-9 can be translated in different reading frames in different bnAbs yet still target the same HA stem pocket. Thus, the D3-9 gene segment in the human immune repertoire can provide a robust defense against influenza virus.</p>
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</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Cell Host Microbe</journal-id>
<journal-id journal-id-type="iso-abbrev">Cell Host Microbe</journal-id>
<journal-title-group><journal-title>Cell Host & Microbe</journal-title>
</journal-title-group>
<issn pub-type="ppub">1931-3128</issn>
<issn pub-type="epub">1934-6069</issn>
<publisher><publisher-name>Elsevier Inc.</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">30308159</article-id>
<article-id pub-id-type="pmc">6327842</article-id>
<article-id pub-id-type="publisher-id">S1931-3128(18)30494-3</article-id>
<article-id pub-id-type="doi">10.1016/j.chom.2018.09.010</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Recurring and Adaptable Binding Motifs in Broadly Neutralizing Antibodies to Influenza Virus Are Encoded on the D3-9 Segment of the Ig Gene</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" id="au1"><name><surname>Wu</surname>
<given-names>Nicholas C.</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author" id="au2"><name><surname>Yamayoshi</surname>
<given-names>Seiya</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au3"><name><surname>Ito</surname>
<given-names>Mutsumi</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au4"><name><surname>Uraki</surname>
<given-names>Ryuta</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au5"><name><surname>Kawaoka</surname>
<given-names>Yoshihiro</given-names>
</name>
<email>yoshihiro.kawaoka@wisc.edu</email>
<xref rid="aff2" ref-type="aff">2</xref>
<xref rid="aff3" ref-type="aff">3</xref>
<xref rid="aff4" ref-type="aff">4</xref>
<xref rid="cor1" ref-type="corresp">∗</xref>
</contrib>
<contrib contrib-type="author" id="au6"><name><surname>Wilson</surname>
<given-names>Ian A.</given-names>
</name>
<email>wilson@scripps.edu</email>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff5" ref-type="aff">5</xref>
<xref rid="fn1" ref-type="fn">6</xref>
<xref rid="cor2" ref-type="corresp">∗∗</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA</aff>
<aff id="aff2"><label>2</label>
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan</aff>
<aff id="aff3"><label>3</label>
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA</aff>
<aff id="aff4"><label>4</label>
Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan</aff>
<aff id="aff5"><label>5</label>
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA</aff>
<author-notes><corresp id="cor1"><label>∗</label>
Corresponding author <email>yoshihiro.kawaoka@wisc.edu</email>
</corresp>
<corresp id="cor2"><label>∗∗</label>
Corresponding author <email>wilson@scripps.edu</email>
</corresp>
<fn id="fn1"><label>6</label>
<p id="ntpara0010">Lead Contact</p>
</fn>
</author-notes>
<pub-date pub-type="pmc-release"><day>10</day>
<month>10</month>
<year>2018</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><day>10</day>
<month>10</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="epub"><day>10</day>
<month>10</month>
<year>2018</year>
</pub-date>
<volume>24</volume>
<issue>4</issue>
<fpage>569</fpage>
<lpage>578.e4</lpage>
<history><date date-type="received"><day>4</day>
<month>6</month>
<year>2018</year>
</date>
<date date-type="rev-recd"><day>16</day>
<month>7</month>
<year>2018</year>
</date>
<date date-type="accepted"><day>13</day>
<month>8</month>
<year>2018</year>
</date>
</history>
<permissions><copyright-statement>© 2018 Elsevier Inc.</copyright-statement>
<copyright-year>2018</copyright-year>
<copyright-holder>Elsevier Inc.</copyright-holder>
<license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p>
</license>
</permissions>
<abstract id="abs0010"><title>Summary</title>
<p>Discovery and characterization of broadly neutralizing antibodies (bnAbs) to the influenza hemagglutinin (HA) stem have provided insights for the development of a universal flu vaccine. Identification of signature features common to bnAbs from different individuals will be key to guiding immunogen design. S9-3-37 is a bnAb isolated from a healthy H5N1 vaccinee. Here, structural characterization reveals that the D3-9 gene segment of S9-3-37 contributes most of the interaction surface with the highly conserved stem epitope on HA. Comparison with other influenza bnAb crystal structures indicates that the D3-9 segment provides a general mechanism for targeting HA stem. Interestingly, such bnAbs can approach the HA stem with vastly different angles and orientations. Moreover, D3-9 can be translated in different reading frames in different bnAbs yet still target the same HA stem pocket. Thus, the D3-9 gene segment in the human immune repertoire can provide a robust defense against influenza virus.</p>
</abstract>
<abstract abstract-type="graphical" id="abs0015"><title>Graphical Abstract</title>
<fig id="undfig1" position="anchor"><graphic xlink:href="fx1_lrg"></graphic>
</fig>
</abstract>
<abstract abstract-type="author-highlights" id="abs0020"><title>Highlights</title>
<p><list list-type="simple" id="ulist0010"><list-item id="u0010"><label>•</label>
<p id="p0010">Structure of bnAb S9-3-37 bound to influenza hemagglutinin stem was determined</p>
</list-item>
<list-item id="u0015"><label>•</label>
<p id="p0015">D3-9-encoded region of S9-3-37 contributes majority of the interaction surface with HA</p>
</list-item>
<list-item id="u0020"><label>•</label>
<p id="p0020">D3-9 gene segment of S9-3-37 can engage the HA stem in two different reading frames</p>
</list-item>
<list-item id="u0025"><label>•</label>
<p id="p0025">D3-9 gene segment represents a recurring mechanism for antibody targeting of HA stem</p>
</list-item>
</list>
</p>
</abstract>
<abstract abstract-type="teaser" id="abs0025"><p>Identifying signature features common to broadly neutralizing antibodies (bnAbs) is key to universal flu vaccine design. Wu et al. report that the D3-9 encoded segment of an influenza hemagglutinin stem-targeting bnAb contributes the majority of the interaction surface and is a recurring motif in antibodies that target the hemagglutinin stem.</p>
</abstract>
<kwd-group id="kwrds0010"><title>Keywords</title>
<kwd>influenza</kwd>
<kwd>broadly neutralizing antibody</kwd>
<kwd>hemagglutinin</kwd>
<kwd>X-ray crystallography</kwd>
<kwd>immune response</kwd>
</kwd-group>
</article-meta>
<notes><p id="misc0010">Published: October 10, 2018</p>
</notes>
</front>
</pmc>
<affiliations><list><country><li>Japon</li>
<li>États-Unis</li>
</country>
<region><li>Californie</li>
<li>Région de Kantō</li>
<li>Wisconsin</li>
</region>
<settlement><li>Madison (Wisconsin)</li>
<li>Tokyo</li>
</settlement>
<orgName><li>Université de Tokyo</li>
<li>Université du Wisconsin à Madison</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Californie"><name sortKey="Wu, Nicholas C" sort="Wu, Nicholas C" uniqKey="Wu N" first="Nicholas C." last="Wu">Nicholas C. Wu</name>
</region>
<name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name>
<name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name>
<name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name>
</country>
<country name="Japon"><region name="Région de Kantō"><name sortKey="Yamayoshi, Seiya" sort="Yamayoshi, Seiya" uniqKey="Yamayoshi S" first="Seiya" last="Yamayoshi">Seiya Yamayoshi</name>
</region>
<name sortKey="Ito, Mutsumi" sort="Ito, Mutsumi" uniqKey="Ito M" first="Mutsumi" last="Ito">Mutsumi Ito</name>
<name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name>
<name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name>
<name sortKey="Uraki, Ryuta" sort="Uraki, Ryuta" uniqKey="Uraki R" first="Ryuta" last="Uraki">Ryuta Uraki</name>
</country>
</tree>
</affiliations>
</record>
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