Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV
Identifieur interne : 000439 ( Pmc/Curation ); précédent : 000438; suivant : 000440Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV
Auteurs : Xiuyuan Ou [République populaire de Chine] ; Yan Liu [République populaire de Chine] ; Xiaobo Lei [République populaire de Chine] ; Pei Li [République populaire de Chine] ; Dan Mi [République populaire de Chine] ; Lili Ren [République populaire de Chine] ; Li Guo [République populaire de Chine] ; Ruixuan Guo [République populaire de Chine] ; Ting Chen [République populaire de Chine] ; Jiaxin Hu [République populaire de Chine] ; Zichun Xiang [République populaire de Chine] ; Zhixia Mu [République populaire de Chine] ; Xing Chen [République populaire de Chine] ; Jieyong Chen [République populaire de Chine] ; Keping Hu [République populaire de Chine] ; Qi Jin [République populaire de Chine] ; Jianwei Wang [République populaire de Chine] ; Zhaohui Qian [République populaire de Chine]Source :
- Nature Communications [ 2041-1723 ] ; 2020.
Abstract
Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.
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DOI: 10.1038/s41467-020-15562-9
PubMed: 32221306
PubMed Central: 7100515
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last="Ou">Xiuyuan Ou</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>NHC Key laboratory of Systems Biology of Pathogens,</institution><institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution></institution-wrap>100176 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100176 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Yan" sort="Liu, Yan" uniqKey="Liu Y" first="Yan" last="Liu">Yan Liu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>NHC Key laboratory of Systems 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uniqKey="Mu Z" first="Zhixia" last="Mu">Zhixia Mu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>NHC Key laboratory of Systems Biology of Pathogens,</institution><institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution></institution-wrap>100176 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100176 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Xing" sort="Chen, Xing" uniqKey="Chen X" first="Xing" last="Chen">Xing Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>Institute of Medicinal Plant Development (IMPLAD),</institution><institution>Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical Collage (PUMC),</institution></institution-wrap>151 Malianwa Road North, Haidian District, 100193 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>151 Malianwa Road North, Haidian District, 100193 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Jieyong" sort="Chen, Jieyong" uniqKey="Chen J" first="Jieyong" last="Chen">Jieyong Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Hengshui Third People’s Hospital, Heibei, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Hengshui Third People’s Hospital, Heibei</wicri:regionArea></affiliation></author><author><name sortKey="Hu, Keping" sort="Hu, Keping" uniqKey="Hu K" first="Keping" last="Hu">Keping Hu</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>Institute of Medicinal Plant Development (IMPLAD),</institution><institution>Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical Collage (PUMC),</institution></institution-wrap>151 Malianwa Road North, Haidian District, 100193 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>151 Malianwa Road North, Haidian District, 100193 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Jin, Qi" sort="Jin, Qi" uniqKey="Jin Q" first="Qi" last="Jin">Qi Jin</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>NHC Key laboratory of Systems Biology of Pathogens,</institution><institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution></institution-wrap>100176 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100176 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Jianwei" sort="Wang, Jianwei" uniqKey="Wang J" first="Jianwei" last="Wang">Jianwei Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>NHC Key laboratory of Systems Biology of Pathogens,</institution><institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution></institution-wrap>100176 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100176 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Qian, Zhaohui" sort="Qian, Zhaohui" uniqKey="Qian Z" first="Zhaohui" last="Qian">Zhaohui Qian</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>NHC Key laboratory of Systems Biology of Pathogens,</institution><institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution></institution-wrap>100176 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100176 Beijing</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ksiazek, Tg" uniqKey="Ksiazek T">TG Ksiazek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM 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uniqKey="Urbanowicz R">RA Urbanowicz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Mk" uniqKey="Wang M">MK Wang</name></author><author><name sortKey="Lim, Sy" uniqKey="Lim S">SY Lim</name></author><author><name sortKey="Lee, Sm" uniqKey="Lee S">SM Lee</name></author><author><name sortKey="Cunningham, Jm" uniqKey="Cunningham J">JM Cunningham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, F" uniqKey="Li F">F Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menachery, Vd" uniqKey="Menachery V">VD Menachery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vorou, Rm" uniqKey="Vorou R">RM Vorou</name></author><author><name sortKey="Papavassiliou, Vg" uniqKey="Papavassiliou V">VG Papavassiliou</name></author><author><name sortKey="Tsiodras, S" uniqKey="Tsiodras S">S 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Nat Commun</journal-id><journal-id journal-id-type="iso-abbrev">Nat Commun</journal-id><journal-title-group><journal-title>Nature Communications</journal-title></journal-title-group><issn pub-type="epub">2041-1723</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32221306</article-id><article-id pub-id-type="pmc">7100515</article-id><article-id pub-id-type="publisher-id">15562</article-id><article-id pub-id-type="doi">10.1038/s41467-020-15562-9</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Ou</surname><given-names>Xiuyuan</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Liu</surname><given-names>Yan</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Lei</surname><given-names>Xiaobo</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Pei</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mi</surname><given-names>Dan</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ren</surname><given-names>Lili</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Guo</surname><given-names>Li</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Guo</surname><given-names>Ruixuan</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Ting</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hu</surname><given-names>Jiaxin</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Xiang</surname><given-names>Zichun</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mu</surname><given-names>Zhixia</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Xing</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Jieyong</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Hu</surname><given-names>Keping</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Jin</surname><given-names>Qi</given-names></name><address><email>jinqi@ipbcams.ac.cn</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-1116-4559</contrib-id><name><surname>Wang</surname><given-names>Jianwei</given-names></name><address><email>wangjw28@163.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-4116-4450</contrib-id><name><surname>Qian</surname><given-names>Zhaohui</given-names></name><address><email>zqian2013@sina.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>NHC Key laboratory of Systems Biology of Pathogens,</institution><institution>Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,</institution></institution-wrap>100176 Beijing, China</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>Institute of Medicinal Plant Development (IMPLAD),</institution><institution>Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical Collage (PUMC),</institution></institution-wrap>151 Malianwa Road North, Haidian District, 100193 Beijing, China</aff><aff id="Aff3"><label>3</label>Hengshui Third People’s Hospital, Heibei, China</aff></contrib-group><pub-date pub-type="epub"><day>27</day><month>3</month><year>2020</year></pub-date><pub-date pub-type="pmc-release"><day>27</day><month>3</month><year>2020</year></pub-date><pub-date pub-type="collection"><year>2020</year></pub-date><volume>11</volume><elocation-id>1620</elocation-id><history><date date-type="received"><day>13</day><month>2</month><year>2020</year></date><date date-type="accepted"><day>16</day><month>3</month><year>2020</year></date></history><permissions><copyright-statement>© The Author(s) 2020</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.</p></abstract><abstract id="Abs2" abstract-type="web-summary"><p id="Par2">SARS-CoV-2 has spread globally. Here, the authors characterize the entry pathway of SARS-CoV-2, show that the SARS-CoV-2 spike protein is less stable than that of SARS-CoV, and show limited cross-neutralization activities between SARS-CoV and SARS-CoV-2 sera.</p></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>Antibodies</kwd><kwd>SARS virus</kwd><kwd>Virus-host interactions</kwd><kwd>Viral infection</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100001809</institution-id><institution>National Natural Science Foundation of China (National Science Foundation of China)</institution></institution-wrap></funding-source><award-id>31970171</award-id><award-id>31670164</award-id><principal-award-recipient><name><surname>Qian</surname><given-names>Zhaohui</given-names></name></principal-award-recipient></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2020</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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