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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Single Amino Acid Substitutions in the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Determine Viral Entry and Immunogenicity of a Major Neutralizing Domain</title><author><name sortKey="Yi, Christopher E" sort="Yi, Christopher E" uniqKey="Yi C" first="Christopher E." last="Yi">Christopher E. Yi</name><affiliation><nlm:aff id="aff0">Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016</nlm:aff></affiliation></author><author><name sortKey="Ba, Lei" sort="Ba, Lei" uniqKey="Ba L" first="Lei" last="Ba">Lei Ba</name><affiliation><nlm:aff id="aff0">Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016</nlm:aff></affiliation></author><author><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name><affiliation><nlm:aff id="aff0">Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016</nlm:aff></affiliation></author><author><name sortKey="Ho, David D" sort="Ho, David D" uniqKey="Ho D" first="David D." last="Ho">David D. Ho</name><affiliation><nlm:aff id="aff0">Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016</nlm:aff></affiliation></author><author><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name><affiliation><nlm:aff id="aff0">Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">16140741</idno><idno type="pmc">1212612</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1212612</idno><idno type="RBID">PMC:1212612</idno><idno type="doi">10.1128/JVI.79.18.11638-11646.2005</idno><date when="2005">2005</date><idno type="wicri:Area/Pmc/Corpus">000697</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000697</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Single Amino Acid Substitutions in the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Determine Viral Entry and Immunogenicity of a Major Neutralizing Domain</title><author><name sortKey="Yi, Christopher E" sort="Yi, Christopher E" uniqKey="Yi C" first="Christopher E." last="Yi">Christopher E. Yi</name><affiliation><nlm:aff id="aff0">Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016</nlm:aff></affiliation></author><author><name sortKey="Ba, Lei" sort="Ba, Lei" uniqKey="Ba L" first="Lei" last="Ba">Lei Ba</name><affiliation><nlm:aff id="aff0">Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016</nlm:aff></affiliation></author><author><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name><affiliation><nlm:aff id="aff0">Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016</nlm:aff></affiliation></author><author><name sortKey="Ho, David D" sort="Ho, David D" uniqKey="Ho D" first="David D." last="Ho">David D. Ho</name><affiliation><nlm:aff id="aff0">Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016</nlm:aff></affiliation></author><author><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name><affiliation><nlm:aff id="aff0">Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016</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="2005">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Neutralizing antibodies (NAbs) against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) spike (S) glycoprotein confer protection to animals experimentally infected with the pathogenic virus. We and others previously demonstrated that a major mechanism for neutralizing SARS-CoV was through blocking the interaction between the S glycoprotein and the cellular receptor angiotensin-converting enzyme 2 (ACE2). In this study, we used in vivo electroporation DNA immunization and a pseudovirus-based assay to functionally evaluate immunogenicity and viral entry. We characterized the neutralization and viral entry determinants within the ACE2-binding domain of the S glycoprotein. The deletion of a positively charged region SΔ(422-463) abolished the capacity of the S glycoprotein to induce NAbs in mice vaccinated by in vivo DNA electroporation. Moreover, the SΔ(422-463) pseudovirus was unable to infect HEK293T-ACE2 cells. To determine the specific residues that contribute to related phenotypes, we replaced eight basic amino acids with alanine. We found that a single amino acid substitution (R441A) in the full-length S DNA vaccine failed to induce NAbs and abolished viral entry when pseudoviruses were generated. However, another substitution (R453A) abolished viral entry while retaining the capacity for inducing NAbs. The difference between R441A and R453A suggests that the determinants for immunogenicity and viral entry may not be identical. Our findings provide direct evidence that these basic residues are essential for immunogenicity of the major neutralizing domain and for viral entry. Our data have implications for the rational design of vaccine and antiviral agents as well as for understanding viral tropism.</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="publisher-id">jvi</journal-id><journal-title>Journal of Virology</journal-title><issn pub-type="ppub">0022-538X</issn><issn pub-type="epub">1098-5514</issn><publisher><publisher-name>American Society for Microbiology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">16140741</article-id><article-id pub-id-type="pmc">1212612</article-id><article-id pub-id-type="publisher-id">0546-05</article-id><article-id pub-id-type="doi">10.1128/JVI.79.18.11638-11646.2005</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject></subj-group></article-categories><title-group><article-title>Single Amino Acid Substitutions in the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Determine Viral Entry and Immunogenicity of a Major Neutralizing Domain</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Yi</surname><given-names>Christopher E.</given-names></name><xref ref-type="aff" rid="aff0"></xref><xref ref-type="fn" rid="fn1">†</xref></contrib><contrib contrib-type="author"><name><surname>Ba</surname><given-names>Lei</given-names></name><xref ref-type="aff" rid="aff0"></xref><xref ref-type="fn" rid="fn1">†</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Linqi</given-names></name><xref ref-type="aff" rid="aff0"></xref></contrib><contrib contrib-type="author"><name><surname>Ho</surname><given-names>David D.</given-names></name><xref ref-type="aff" rid="aff0"></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Zhiwei</given-names></name><xref ref-type="aff" rid="aff0"></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="aff0">Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016</aff><author-notes><fn id="cor1"><label>*</label><p>Corresponding author. Mailing address: Aaron Diamond AIDS Research Center, The Rockefeller University, 455 1st Avenue, 7th Floor, New York, NY 10016. Phone: (212) 448-5031. Fax: (212) 725-1126. E-mail: <email>zchen@adarc.org</email>.</p></fn><fn id="fn1"><label>†</label><p>These authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="ppub"><month>9</month><year>2005</year></pub-date><volume>79</volume><issue>18</issue><fpage>11638</fpage><lpage>11646</lpage><history><date date-type="received"><day>16</day><month>3</month><year>2005</year></date><date date-type="accepted"><day>29</day><month>6</month><year>2005</year></date></history><copyright-statement>Copyright © 2005, American Society for Microbiology</copyright-statement><copyright-year>2005</copyright-year><abstract><p>Neutralizing antibodies (NAbs) against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) spike (S) glycoprotein confer protection to animals experimentally infected with the pathogenic virus. We and others previously demonstrated that a major mechanism for neutralizing SARS-CoV was through blocking the interaction between the S glycoprotein and the cellular receptor angiotensin-converting enzyme 2 (ACE2). In this study, we used in vivo electroporation DNA immunization and a pseudovirus-based assay to functionally evaluate immunogenicity and viral entry. We characterized the neutralization and viral entry determinants within the ACE2-binding domain of the S glycoprotein. The deletion of a positively charged region SΔ(422-463) abolished the capacity of the S glycoprotein to induce NAbs in mice vaccinated by in vivo DNA electroporation. Moreover, the SΔ(422-463) pseudovirus was unable to infect HEK293T-ACE2 cells. To determine the specific residues that contribute to related phenotypes, we replaced eight basic amino acids with alanine. We found that a single amino acid substitution (R441A) in the full-length S DNA vaccine failed to induce NAbs and abolished viral entry when pseudoviruses were generated. However, another substitution (R453A) abolished viral entry while retaining the capacity for inducing NAbs. The difference between R441A and R453A suggests that the determinants for immunogenicity and viral entry may not be identical. Our findings provide direct evidence that these basic residues are essential for immunogenicity of the major neutralizing domain and for viral entry. Our data have implications for the rational design of vaccine and antiviral agents as well as for understanding viral tropism.</p></abstract><custom-meta-wrap><custom-meta><meta-name>PDF filename</meta-name><meta-value>zjv01805011638</meta-value></custom-meta></custom-meta-wrap></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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