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 : 000361 ( PascalFrancis/Checkpoint ); précédent : 000360; suivant : 000362Natural 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.
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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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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">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</title>
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<wicri:noRegion>New York, New York 100161</wicri:noRegion>
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<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>
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<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>
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<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>
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<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>
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<fA03 i2="1"><s0>J. virol.</s0>
</fA03>
<fA05><s2>81</s2>
</fA05>
<fA06><s2>9</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>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</s1>
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<fA11 i1="01" i2="1"><s1>LI LIU</s1>
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<fA11 i1="02" i2="1"><s1>QING FANG</s1>
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<fA11 i1="04" i2="1"><s1>HANZHONG WANG</s1>
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<fA11 i1="05" i2="1"><s1>YI (Christopher E.)</s1>
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<fA11 i1="06" i2="1"><s1>LEI BA</s1>
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<fA11 i1="07" i2="1"><s1>WENJIE YU</s1>
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<fA11 i1="08" i2="1"><s1>LIN (Richard D.)</s1>
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<fA11 i1="09" i2="1"><s1>TAISHENG LI</s1>
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<fA11 i1="10" i2="1"><s1>ZHIHONG HU</s1>
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<fA11 i1="11" i2="1"><s1>HO (David D.)</s1>
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<fA11 i1="12" i2="1"><s1>LINQI ZHANG</s1>
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<fA11 i1="13" i2="1"><s1>ZHIWEI CHEN</s1>
</fA11>
<fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1>
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<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>
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<fA14 i1="02"><s1>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences</s1>
<s2>Hubei 430071</s2>
<s3>CHN</s3>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<fA14 i1="03"><s1>AIDS Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College</s1>
<s2>Beijing 100730</s2>
<s3>CHN</s3>
<sZ>9 aut.</sZ>
<sZ>12 aut.</sZ>
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<fA20><s1>4694-4700</s1>
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<fA60><s1>P</s1>
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<fA61><s0>A</s0>
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<fC01 i1="01" l="ENG"><s0>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.</s0>
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