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 : 003654 ( Main/Exploration ); précédent : 003653; suivant : 003655Natural 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 ; Qing Fang ; Fei Deng ; Hanzhong Wang ; Christopher E. Yi ; Lei Ba ; Wenjie Yu ; Richard D. Lin ; Taisheng Li ; Zhihong Hu ; David D. Ho ; Linqi Zhang ; Zhiwei ChenSource :
- Journal of Virology [ 0022-538X ] ; 2007.
Descripteurs français
- KwdFr :
- Analyse de regroupements, Analyse de séquence d'ADN, Chine, Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (métabolisme), Mutation (génétique), Phylogénie, Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (métabolisme), RT-PCR, Réactions croisées (génétique), Réactions croisées (immunologie), Structure tertiaire des protéines, Séquence nucléotidique, Tests de neutralisation, Virus du SRAS (génétique).
- MESH :
- génétique : Glycoprotéines membranaires, Mutation, Protéines de l'enveloppe virale, Réactions croisées, Virus du SRAS.
- immunologie : Réactions croisées.
- métabolisme : Glycoprotéines membranaires, Protéines de l'enveloppe virale.
- Analyse de regroupements, Analyse de séquence d'ADN, Chine, Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Phylogénie, RT-PCR, Structure tertiaire des protéines, Séquence nucléotidique, Tests de neutralisation.
- Wicri :
- geographic : République populaire de Chine.
English descriptors
- KwdEn :
- Base Sequence, China, Cluster Analysis, Cross Reactions (genetics), Cross Reactions (immunology), Membrane Glycoproteins (genetics), Membrane Glycoproteins (metabolism), Molecular Sequence Data, Mutation (genetics), Neutralization Tests, Phylogeny, Protein Structure, Tertiary, Reverse Transcriptase Polymerase Chain Reaction, SARS Virus (genetics), Sequence Analysis, DNA, Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (genetics), Viral Envelope Proteins (metabolism).
- MESH :
- chemical , genetics : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , metabolism : Membrane Glycoproteins, Viral Envelope Proteins.
- geographic : China, Spike Glycoprotein, Coronavirus.
- genetics : Cross Reactions, Mutation, SARS Virus.
- immunology : Cross Reactions.
- Base Sequence, Cluster Analysis, Molecular Sequence Data, Neutralization Tests, Phylogeny, Protein Structure, Tertiary, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA.
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.
Url:
DOI: 10.1128/JVI.02389-06
PubMed: 17314167
PubMed Central: 1900161
Affiliations:
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Le document en format XML
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<series><title level="j">Journal of Virology</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Base Sequence</term>
<term>China</term>
<term>Cluster Analysis</term>
<term>Cross Reactions (genetics)</term>
<term>Cross Reactions (immunology)</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Molecular Sequence Data</term>
<term>Mutation (genetics)</term>
<term>Neutralization Tests</term>
<term>Phylogeny</term>
<term>Protein Structure, Tertiary</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>SARS Virus (genetics)</term>
<term>Sequence Analysis, DNA</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de regroupements</term>
<term>Analyse de séquence d'ADN</term>
<term>Chine</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
<term>Mutation (génétique)</term>
<term>Phylogénie</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>RT-PCR</term>
<term>Réactions croisées (génétique)</term>
<term>Réactions croisées (immunologie)</term>
<term>Structure tertiaire des protéines</term>
<term>Séquence nucléotidique</term>
<term>Tests de neutralisation</term>
<term>Virus du SRAS (génétique)</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Membrane Glycoproteins</term>
<term>Viral Envelope Proteins</term>
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<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Membrane Glycoproteins</term>
<term>Viral Envelope Proteins</term>
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<term>Spike Glycoprotein, Coronavirus</term>
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<term>Mutation</term>
<term>SARS Virus</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéines membranaires</term>
<term>Mutation</term>
<term>Protéines de l'enveloppe virale</term>
<term>Réactions croisées</term>
<term>Virus du SRAS</term>
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<front><div type="abstract" xml:lang="en"><p>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.</p>
</div>
</front>
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<affiliations><list></list>
<tree><noCountry><name sortKey="Ba, Lei" sort="Ba, Lei" uniqKey="Ba L" first="Lei" last="Ba">Lei Ba</name>
<name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name>
<name sortKey="Deng, Fei" sort="Deng, Fei" uniqKey="Deng F" first="Fei" last="Deng">Fei Deng</name>
<name sortKey="Fang, Qing" sort="Fang, Qing" uniqKey="Fang Q" first="Qing" last="Fang">Qing Fang</name>
<name sortKey="Ho, David D" sort="Ho, David D" uniqKey="Ho D" first="David D." last="Ho">David D. Ho</name>
<name sortKey="Hu, Zhihong" sort="Hu, Zhihong" uniqKey="Hu Z" first="Zhihong" last="Hu">Zhihong Hu</name>
<name sortKey="Li, Taisheng" sort="Li, Taisheng" uniqKey="Li T" first="Taisheng" last="Li">Taisheng Li</name>
<name sortKey="Lin, Richard D" sort="Lin, Richard D" uniqKey="Lin R" first="Richard D." last="Lin">Richard D. Lin</name>
<name sortKey="Liu, Li" sort="Liu, Li" uniqKey="Liu L" first="Li" last="Liu">Li Liu</name>
<name sortKey="Wang, Hanzhong" sort="Wang, Hanzhong" uniqKey="Wang H" first="Hanzhong" last="Wang">Hanzhong Wang</name>
<name sortKey="Yi, Christopher E" sort="Yi, Christopher E" uniqKey="Yi C" first="Christopher E." last="Yi">Christopher E. Yi</name>
<name sortKey="Yu, Wenjie" sort="Yu, Wenjie" uniqKey="Yu W" first="Wenjie" last="Yu">Wenjie Yu</name>
<name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name>
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