Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus
Identifieur interne : 003B50 ( Main/Curation ); précédent : 003B49; suivant : 003B51Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus
Auteurs : LI LIU [États-Unis] ; QING FANG [États-Unis] ; FEI DENG [République populaire de Chine] ; HANZHONG WANG [République populaire de Chine] ; Christopher E. Yi [États-Unis] ; LEI BA [États-Unis] ; WENJIE YU [États-Unis] ; Richard D. Lin [États-Unis] ; TAISHENG LI [République populaire de Chine] ; ZHIHONG HU [République populaire de Chine] ; David D. Ho [États-Unis] ; LINQI ZHANG [États-Unis, République populaire de Chine] ; ZHIWEI CHEN [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2007.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
The severe acute respiratory syndrome (SARS) outbreak of 2002 and 2003 occurred as a result of zoonotic transmission. Coronavirus (CoV) found in naturally infected palm civet (civet-CoV) represents the closest genetic relative to SARS-CoV, but the degree and the determinants of cross-neutralization among these viruses remain to be investigated. Studies indicate that the receptor binding domain (RBD) of the SARS-CoV spike (S) glycoprotein contains major determinants for viral entry and neutralization. We aim to characterize the impact of natural mutations within the RBDs of civet-CoVs on viral entry and cross-neutralization. In this study, the S glycoprotein genes were recovered from naturally infected civets in central China (Hubei province), extending the geographic distribution of civet-CoV beyond the southeastern province of Guangdong. Moreover, pseudoviruses generated in our laboratory with four civet S genes, each with a distinct RBD, infected cells expressing human receptor angiotensin-converting enzyme 2, but with 90 to 95% less efficiency compared to that of SARS-CoV. These four civet S genes were also constructed as DNA vaccines to immunize mice. Immunized sera elicited against most civet S glycoproteins displayed potent neutralizing activities against autologous viruses but were much less efficient (50% inhibitory concentration, 20- to 40-fold) at neutralizing SARS-CoV and vice versa. Convalescence-phase sera from humans were similarly ineffective against the dominant civet pseudovirus. Our findings suggest that the design of SARS vaccine should consider not only preventing the reemergence of SARS-CoV but also providing cross-protection, thus interrupting zoonotic transmission of a group of genetically divergent civet CoVs of broad geographic origin.
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Pascal:07-0245100Le document en format XML
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<author><name sortKey="Zhiwei Chen" sort="Zhiwei Chen" uniqKey="Zhiwei Chen" last="Zhiwei Chen">ZHIWEI CHEN</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1>
<s2>New York, New York 100161</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>New York, New York 100161</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
<idno type="ISSN">0022-538X</idno>
<imprint><date when="2007">2007</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
<idno type="ISSN">0022-538X</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus</term>
<term>Cross reaction</term>
<term>Glycoprotein</term>
<term>Mutation</term>
<term>Neutralization</term>
<term>Severe acute respiratory syndrome</term>
<term>Virology</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term>
<term>Mutation</term>
<term>Glycoprotéine</term>
<term>Réaction croisée</term>
<term>Neutralisation</term>
<term>Virologie</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The severe acute respiratory syndrome (SARS) outbreak of 2002 and 2003 occurred as a result of zoonotic transmission. Coronavirus (CoV) found in naturally infected palm civet (civet-CoV) represents the closest genetic relative to SARS-CoV, but the degree and the determinants of cross-neutralization among these viruses remain to be investigated. Studies indicate that the receptor binding domain (RBD) of the SARS-CoV spike (S) glycoprotein contains major determinants for viral entry and neutralization. We aim to characterize the impact of natural mutations within the RBDs of civet-CoVs on viral entry and cross-neutralization. In this study, the S glycoprotein genes were recovered from naturally infected civets in central China (Hubei province), extending the geographic distribution of civet-CoV beyond the southeastern province of Guangdong. Moreover, pseudoviruses generated in our laboratory with four civet S genes, each with a distinct RBD, infected cells expressing human receptor angiotensin-converting enzyme 2, but with 90 to 95% less efficiency compared to that of SARS-CoV. These four civet S genes were also constructed as DNA vaccines to immunize mice. Immunized sera elicited against most civet S glycoproteins displayed potent neutralizing activities against autologous viruses but were much less efficient (50% inhibitory concentration, 20- to 40-fold) at neutralizing SARS-CoV and vice versa. Convalescence-phase sera from humans were similarly ineffective against the dominant civet pseudovirus. Our findings suggest that the design of SARS vaccine should consider not only preventing the reemergence of SARS-CoV but also providing cross-protection, thus interrupting zoonotic transmission of a group of genetically divergent civet CoVs of broad geographic origin.</div>
</front>
</TEI>
</record>
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