S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients
Identifieur interne : 005A72 ( Main/Exploration ); précédent : 005A71; suivant : 005A73S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients
Auteurs : Heike Hofmann [Allemagne] ; Kim Hattermann [Allemagne] ; Andrea Marzi [Allemagne] ; Thomas Gramberg [Allemagne] ; Martina Geier [Allemagne] ; Mandy Krumbiegel [Allemagne] ; Seraphin Kuate [Allemagne] ; Klaus Überla [Allemagne] ; Matthias Niedrig [Allemagne] ; Stefan Pöhlmann [Allemagne]Source :
- Journal of virology [ 0022-538X ] ; 2004.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps antiviraux (sang), Carcinome hépatocellulaire, Foie (cytologie), Foie (virologie), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (immunologie), Glycoprotéines membranaires (métabolisme), Humains, Lapins, Lentivirus (génétique), Lignée cellulaire, Lignée cellulaire tumorale, Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (immunologie), Protéines de l'enveloppe virale (métabolisme), Rein (cytologie), Rein (virologie), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (virologie), Tests de neutralisation, Transfection, Tumeurs du foie, Virion, Virus du SRAS (pathogénicité).
- MESH :
- cytologie : Foie, Rein.
- génétique : Glycoprotéines membranaires, Lentivirus, Protéines de l'enveloppe virale.
- immunologie : Anticorps antiviraux, Glycoprotéines membranaires, Protéines de l'enveloppe virale, Syndrome respiratoire aigu sévère.
- métabolisme : Glycoprotéines membranaires, Protéines de l'enveloppe virale.
- pathogénicité : Virus du SRAS.
- sang : Anticorps antiviraux.
- virologie : Foie, Rein, Syndrome respiratoire aigu sévère.
- Pascal (Inist)
- Animaux, Carcinome hépatocellulaire, Coronavirus, Glycoprotéine de spicule des coronavirus, Homme, Humains, Lapins, Lignée cellulaire, Lignée cellulaire tumorale, Tests de neutralisation, Transfection, Tumeurs du foie, Virion, Vitronectine, Protéine, Lignée cellulaire, Cellule cible, Anticorps neutralisant, Neutralisation, Infection, Microbiologie, Syndrome respiratoire aigu sévère, Carcinome hépatocellulaire, Virologie.
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Animals, Antibodies, Viral (blood), Antibodies, Viral (immunology), Carcinoma, Hepatocellular, Cell Line, Cell Line, Tumor, Cell line, Coronavirus, Hepatocellular carcinoma, Human, Humans, Infection, Kidney (cytology), Kidney (virology), Lentivirus (genetics), Liver (cytology), Liver (virology), Liver Neoplasms, Membrane Glycoproteins (genetics), Membrane Glycoproteins (immunology), Membrane Glycoproteins (metabolism), Microbiology, Neutralization, Neutralization Tests, Neutralizing antibody, Protein, Rabbits, SARS Virus (pathogenicity), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (virology), Severe acute respiratory syndrome, Spike Glycoprotein, Coronavirus, Target cell, Transfection, Viral Envelope Proteins (genetics), Viral Envelope Proteins (immunology), Viral Envelope Proteins (metabolism), Virion, Virology, Vitronectin.
- MESH :
- chemical , blood : Antibodies, Viral.
- chemical , genetics : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , immunology : Antibodies, Viral, Membrane Glycoproteins, Viral Envelope Proteins.
- cytology : Kidney, Liver.
- genetics : Lentivirus.
- immunology : Severe Acute Respiratory Syndrome.
- chemical , metabolism : Membrane Glycoproteins, Viral Envelope Proteins.
- pathogenicity : SARS Virus.
- virology : Kidney, Liver, Severe Acute Respiratory Syndrome.
- Animals, Carcinoma, Hepatocellular, Cell Line, Cell Line, Tumor, Humans, Liver Neoplasms, Neutralization Tests, Rabbits, Spike Glycoprotein, Coronavirus, Transfection, Virion.
Abstract
The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes severe pneumonia with a fatal outcome in approximately 10% of patients. SARS-CoV is not closely related to other coronaviruses but shares a similar genome organization. Entry of coronaviruses into target cells is mediated by the viral S protein. We functionally analyzed SARS-CoV S using pseudotyped lentiviral particles (pseudotypes). The SARS-CoV S protein was found to be expressed at the cell surface upon transient transfection. Coexpression of SARS-CoV S with human immunodeficiency virus-based reporter constructs yielded viruses that were infectious for a range of cell lines. Most notably, viral pseudotypes harboring SARS-CoV S infected hepatoma cell lines but not T- and B-cell lines. Infection of the hepatoma cell line Huh-7 was also observed with replication-competent SARS-CoV, indicating that hepatocytes might be targeted by SARS-CoV in vivo. Inhibition of vacuolar acidification impaired infection by SARS-CoV S-bearing pseudotypes, indicating that S-mediated entry requires low pH. Finally, infection by SARS-CoV S pseudotypes but not by vesicular stomatitis virus G pseudotypes was efficiently inhibited by a rabbit serum raised against SARS-CoV particles and by sera from SARS patients, demonstrating that SARS-CoV S is a target for neutralizing antibodies and that such antibodies are generated in SARS-CoV-infected patients. Our results show that viral pseudotyping can be employed for the analysis of SARS-CoV S function. Moreover, we provide evidence that SARS-CoV infection might not be limited to lung tissue and can be inhibited by the humoral immune response in infected patients.
Url:
Affiliations:
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Le document en format XML
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<author><name sortKey="Marzi, Andrea" sort="Marzi, Andrea" uniqKey="Marzi A" first="Andrea" last="Marzi">Andrea Marzi</name>
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<region type="district" nuts="2">District de Moyenne-Franconie</region>
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<region type="district" nuts="2">District de Moyenne-Franconie</region>
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</affiliation>
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<region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Moyenne-Franconie</region>
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</affiliation>
</author>
<author><name sortKey="Krumbiegel, Mandy" sort="Krumbiegel, Mandy" uniqKey="Krumbiegel M" first="Mandy" last="Krumbiegel">Mandy Krumbiegel</name>
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<country>Allemagne</country>
<wicri:noRegion>91054 Erlangen</wicri:noRegion>
<placeName><settlement type="city">Erlangen</settlement>
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<region type="district" nuts="2">District de Moyenne-Franconie</region>
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<author><name sortKey="Kuate, Seraphin" sort="Kuate, Seraphin" uniqKey="Kuate S" first="Seraphin" last="Kuate">Seraphin Kuate</name>
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<s3>DEU</s3>
<sZ>7 aut.</sZ>
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<country>Allemagne</country>
<wicri:noRegion>44801 Bochum</wicri:noRegion>
<wicri:noRegion>Ruhr University Bochum</wicri:noRegion>
<wicri:noRegion>44801 Bochum</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Uberla, Klaus" sort="Uberla, Klaus" uniqKey="Uberla K" first="Klaus" last="Überla">Klaus Überla</name>
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<country>Allemagne</country>
<wicri:noRegion>44801 Bochum</wicri:noRegion>
<wicri:noRegion>Ruhr University Bochum</wicri:noRegion>
<wicri:noRegion>44801 Bochum</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Niedrig, Matthias" sort="Niedrig, Matthias" uniqKey="Niedrig M" first="Matthias" last="Niedrig">Matthias Niedrig</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Robert Koch Institute</s1>
<s2>13353 Berlin</s2>
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<country>Allemagne</country>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
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</affiliation>
</author>
<author><name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg</s1>
<s2>91054 Erlangen</s2>
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<country>Allemagne</country>
<wicri:noRegion>91054 Erlangen</wicri:noRegion>
<placeName><settlement type="city">Erlangen</settlement>
<region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Moyenne-Franconie</region>
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<country>Allemagne</country>
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<region type="district" nuts="2">District de Moyenne-Franconie</region>
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</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="2004">2004</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>
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<term>Antibodies, Viral (blood)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Carcinoma, Hepatocellular</term>
<term>Cell Line</term>
<term>Cell Line, Tumor</term>
<term>Cell line</term>
<term>Coronavirus</term>
<term>Hepatocellular carcinoma</term>
<term>Human</term>
<term>Humans</term>
<term>Infection</term>
<term>Kidney (cytology)</term>
<term>Kidney (virology)</term>
<term>Lentivirus (genetics)</term>
<term>Liver (cytology)</term>
<term>Liver (virology)</term>
<term>Liver Neoplasms</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Microbiology</term>
<term>Neutralization</term>
<term>Neutralization Tests</term>
<term>Neutralizing antibody</term>
<term>Protein</term>
<term>Rabbits</term>
<term>SARS Virus (pathogenicity)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Severe acute respiratory syndrome</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Target cell</term>
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<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Viral Envelope Proteins (metabolism)</term>
<term>Virion</term>
<term>Virology</term>
<term>Vitronectin</term>
</keywords>
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<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps antiviraux (sang)</term>
<term>Carcinome hépatocellulaire</term>
<term>Foie (cytologie)</term>
<term>Foie (virologie)</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
<term>Humains</term>
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<term>Lentivirus (génétique)</term>
<term>Lignée cellulaire</term>
<term>Lignée cellulaire tumorale</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>Rein (cytologie)</term>
<term>Rein (virologie)</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Tests de neutralisation</term>
<term>Transfection</term>
<term>Tumeurs du foie</term>
<term>Virion</term>
<term>Virus du SRAS (pathogénicité)</term>
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<term>Membrane Glycoproteins</term>
<term>Viral Envelope Proteins</term>
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<term>Rein</term>
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<term>Liver</term>
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<term>Viral Envelope Proteins</term>
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<term>Protéines de l'enveloppe virale</term>
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<term>Rein</term>
<term>Syndrome respiratoire aigu sévère</term>
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<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Kidney</term>
<term>Liver</term>
<term>Severe Acute Respiratory Syndrome</term>
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<term>Carcinoma, Hepatocellular</term>
<term>Cell Line</term>
<term>Cell Line, Tumor</term>
<term>Humans</term>
<term>Liver Neoplasms</term>
<term>Neutralization Tests</term>
<term>Rabbits</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Transfection</term>
<term>Virion</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term>
<term>Carcinome hépatocellulaire</term>
<term>Coronavirus</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Homme</term>
<term>Humains</term>
<term>Lapins</term>
<term>Lignée cellulaire</term>
<term>Lignée cellulaire tumorale</term>
<term>Tests de neutralisation</term>
<term>Transfection</term>
<term>Tumeurs du foie</term>
<term>Virion</term>
<term>Vitronectine</term>
<term>Protéine</term>
<term>Lignée cellulaire</term>
<term>Cellule cible</term>
<term>Anticorps neutralisant</term>
<term>Neutralisation</term>
<term>Infection</term>
<term>Microbiologie</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Carcinome hépatocellulaire</term>
<term>Virologie</term>
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<front><div type="abstract" xml:lang="en">The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes severe pneumonia with a fatal outcome in approximately 10% of patients. SARS-CoV is not closely related to other coronaviruses but shares a similar genome organization. Entry of coronaviruses into target cells is mediated by the viral S protein. We functionally analyzed SARS-CoV S using pseudotyped lentiviral particles (pseudotypes). The SARS-CoV S protein was found to be expressed at the cell surface upon transient transfection. Coexpression of SARS-CoV S with human immunodeficiency virus-based reporter constructs yielded viruses that were infectious for a range of cell lines. Most notably, viral pseudotypes harboring SARS-CoV S infected hepatoma cell lines but not T- and B-cell lines. Infection of the hepatoma cell line Huh-7 was also observed with replication-competent SARS-CoV, indicating that hepatocytes might be targeted by SARS-CoV in vivo. Inhibition of vacuolar acidification impaired infection by SARS-CoV S-bearing pseudotypes, indicating that S-mediated entry requires low pH. Finally, infection by SARS-CoV S pseudotypes but not by vesicular stomatitis virus G pseudotypes was efficiently inhibited by a rabbit serum raised against SARS-CoV particles and by sera from SARS patients, demonstrating that SARS-CoV S is a target for neutralizing antibodies and that such antibodies are generated in SARS-CoV-infected patients. Our results show that viral pseudotyping can be employed for the analysis of SARS-CoV S function. Moreover, we provide evidence that SARS-CoV infection might not be limited to lung tissue and can be inhibited by the humoral immune response in infected patients.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
</country>
<region><li>Bavière</li>
<li>Berlin</li>
<li>District de Moyenne-Franconie</li>
</region>
<settlement><li>Berlin</li>
<li>Erlangen</li>
</settlement>
</list>
<tree><country name="Allemagne"><region name="Bavière"><name sortKey="Hofmann, Heike" sort="Hofmann, Heike" uniqKey="Hofmann H" first="Heike" last="Hofmann">Heike Hofmann</name>
</region>
<name sortKey="Geier, Martina" sort="Geier, Martina" uniqKey="Geier M" first="Martina" last="Geier">Martina Geier</name>
<name sortKey="Geier, Martina" sort="Geier, Martina" uniqKey="Geier M" first="Martina" last="Geier">Martina Geier</name>
<name sortKey="Gramberg, Thomas" sort="Gramberg, Thomas" uniqKey="Gramberg T" first="Thomas" last="Gramberg">Thomas Gramberg</name>
<name sortKey="Gramberg, Thomas" sort="Gramberg, Thomas" uniqKey="Gramberg T" first="Thomas" last="Gramberg">Thomas Gramberg</name>
<name sortKey="Hattermann, Kim" sort="Hattermann, Kim" uniqKey="Hattermann K" first="Kim" last="Hattermann">Kim Hattermann</name>
<name sortKey="Hofmann, Heike" sort="Hofmann, Heike" uniqKey="Hofmann H" first="Heike" last="Hofmann">Heike Hofmann</name>
<name sortKey="Krumbiegel, Mandy" sort="Krumbiegel, Mandy" uniqKey="Krumbiegel M" first="Mandy" last="Krumbiegel">Mandy Krumbiegel</name>
<name sortKey="Krumbiegel, Mandy" sort="Krumbiegel, Mandy" uniqKey="Krumbiegel M" first="Mandy" last="Krumbiegel">Mandy Krumbiegel</name>
<name sortKey="Kuate, Seraphin" sort="Kuate, Seraphin" uniqKey="Kuate S" first="Seraphin" last="Kuate">Seraphin Kuate</name>
<name sortKey="Marzi, Andrea" sort="Marzi, Andrea" uniqKey="Marzi A" first="Andrea" last="Marzi">Andrea Marzi</name>
<name sortKey="Marzi, Andrea" sort="Marzi, Andrea" uniqKey="Marzi A" first="Andrea" last="Marzi">Andrea Marzi</name>
<name sortKey="Niedrig, Matthias" sort="Niedrig, Matthias" uniqKey="Niedrig M" first="Matthias" last="Niedrig">Matthias Niedrig</name>
<name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name>
<name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name>
<name sortKey="Uberla, Klaus" sort="Uberla, Klaus" uniqKey="Uberla K" first="Klaus" last="Überla">Klaus Überla</name>
</country>
</tree>
</affiliations>
</record>
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