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 : 000876 ( PascalFrancis/Corpus ); précédent : 000875; suivant : 000877S 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 ; Kim Hattermann ; Andrea Marzi ; Thomas Gramberg ; Martina Geier ; Mandy Krumbiegel ; Seraphin Kuate ; Klaus Überla ; Matthias Niedrig ; Stefan PöhlmannSource :
- Journal of virology [ 0022-538X ] ; 2004.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
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.
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NO : | PASCAL 04-0316775 INIST |
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ET : | S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients |
AU : | HOFMANN (Heike); HATTERMANN (Kim); MARZI (Andrea); GRAMBERG (Thomas); GEIER (Martina); KRUMBIEGEL (Mandy); KUATE (Seraphin); ÜBERLA (Klaus); NIEDRIG (Matthias); PÖHLMANN (Stefan) |
AF : | Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg/91054 Erlangen/Allemagne (1 aut., 3 aut., 4 aut., 5 aut., 6 aut., 10 aut.); Nikolaus-Fiebiger-Center, University Erlangen-Nürnberg/91054 Erlangen/Allemagne (1 aut., 3 aut., 4 aut., 5 aut., 6 aut., 10 aut.); Robert Koch Institute/13353 Berlin/Allemagne (2 aut., 9 aut.); Department for Molecular and Medical Virology, Ruhr University Bochum/44801 Bochum/Allemagne (7 aut., 8 aut.) |
DT : | Publication en série; Niveau analytique |
SO : | Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2004; Vol. 78; No. 12; Pp. 6134-6142; Bibl. 75 ref. |
LA : | Anglais |
EA : | 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. |
CC : | 002A05C10; 002B04 |
FD : | Coronavirus; Homme; Vitronectine; Protéine; Lignée cellulaire; Cellule cible; Anticorps neutralisant; Neutralisation; Infection; Microbiologie; Syndrome respiratoire aigu sévère; Carcinome hépatocellulaire; Virologie |
FG : | Coronaviridae; Nidovirales; Virus; Virose; Appareil respiratoire pathologie; Poumon pathologie; Appareil digestif pathologie; Foie pathologie; Tumeur maligne |
ED : | Coronavirus; Human; Vitronectin; Protein; Cell line; Target cell; Neutralizing antibody; Neutralization; Infection; Microbiology; Severe acute respiratory syndrome; Hepatocellular carcinoma; Virology |
EG : | Coronaviridae; Nidovirales; Virus; Viral disease; Respiratory disease; Lung disease; Digestive diseases; Hepatic disease; Malignant tumor |
SD : | Coronavirus; Hombre; Vitronectina; Proteína; Línea celular; Célula blanco; anticuerpo neutralizante; Neutralización; Infección; Microbiología; Síndrome respiratorio agudo severo; Carcinoma hepatocelular; Virología |
LO : | INIST-13592.354000112010850060 |
ID : | 04-0316775 |
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Pascal:04-0316775Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients</title>
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<term>Coronavirus</term>
<term>Hepatocellular carcinoma</term>
<term>Human</term>
<term>Infection</term>
<term>Microbiology</term>
<term>Neutralization</term>
<term>Neutralizing antibody</term>
<term>Protein</term>
<term>Severe acute respiratory syndrome</term>
<term>Target cell</term>
<term>Virology</term>
<term>Vitronectin</term>
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<term>Homme</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>
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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>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0022-538X</s0>
</fA01>
<fA03 i2="1"><s0>J. virol.</s0>
</fA03>
<fA05><s2>78</s2>
</fA05>
<fA06><s2>12</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>HOFMANN (Heike)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>HATTERMANN (Kim)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>MARZI (Andrea)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>GRAMBERG (Thomas)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>GEIER (Martina)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>KRUMBIEGEL (Mandy)</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>KUATE (Seraphin)</s1>
</fA11>
<fA11 i1="08" i2="1"><s1>ÜBERLA (Klaus)</s1>
</fA11>
<fA11 i1="09" i2="1"><s1>NIEDRIG (Matthias)</s1>
</fA11>
<fA11 i1="10" i2="1"><s1>PÖHLMANN (Stefan)</s1>
</fA11>
<fA14 i1="01"><s1>Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg</s1>
<s2>91054 Erlangen</s2>
<s3>DEU</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>10 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>Nikolaus-Fiebiger-Center, University Erlangen-Nürnberg</s1>
<s2>91054 Erlangen</s2>
<s3>DEU</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>10 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>Robert Koch Institute</s1>
<s2>13353 Berlin</s2>
<s3>DEU</s3>
<sZ>2 aut.</sZ>
<sZ>9 aut.</sZ>
</fA14>
<fA14 i1="04"><s1>Department for Molecular and Medical Virology, Ruhr University Bochum</s1>
<s2>44801 Bochum</s2>
<s3>DEU</s3>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
</fA14>
<fA20><s1>6134-6142</s1>
</fA20>
<fA21><s1>2004</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>13592</s2>
<s5>354000112010850060</s5>
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<fA44><s0>0000</s0>
<s1>© 2004 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>75 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>04-0316775</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Journal of virology</s0>
</fA64>
<fA66 i1="01"><s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>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.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002A05C10</s0>
</fC02>
<fC02 i1="02" i2="X"><s0>002B04</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Coronavirus</s0>
<s2>NW</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Coronavirus</s0>
<s2>NW</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Coronavirus</s0>
<s2>NW</s2>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Homme</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Human</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Hombre</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Vitronectine</s0>
<s5>05</s5>
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<s5>05</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Vitronectina</s0>
<s5>05</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Protéine</s0>
<s5>06</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Protein</s0>
<s5>06</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Proteína</s0>
<s5>06</s5>
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<fC03 i1="05" i2="X" l="FRE"><s0>Lignée cellulaire</s0>
<s5>07</s5>
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<fC03 i1="05" i2="X" l="ENG"><s0>Cell line</s0>
<s5>07</s5>
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<s5>07</s5>
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<fC03 i1="06" i2="X" l="FRE"><s0>Cellule cible</s0>
<s5>08</s5>
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<s5>08</s5>
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<fC03 i1="06" i2="X" l="SPA"><s0>Célula blanco</s0>
<s5>08</s5>
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<fC03 i1="07" i2="X" l="FRE"><s0>Anticorps neutralisant</s0>
<s5>09</s5>
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<s5>09</s5>
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<fC03 i1="07" i2="X" l="SPA"><s0>anticuerpo neutralizante</s0>
<s5>09</s5>
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<s5>10</s5>
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<s5>10</s5>
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<fC03 i1="08" i2="X" l="SPA"><s0>Neutralización</s0>
<s5>10</s5>
</fC03>
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<s2>NM</s2>
<s5>11</s5>
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<s2>NM</s2>
<s5>11</s5>
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<s2>NM</s2>
<s5>11</s5>
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<s5>12</s5>
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<s5>12</s5>
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<fC03 i1="11" i2="X" l="FRE"><s0>Syndrome respiratoire aigu sévère</s0>
<s2>NM</s2>
<s5>14</s5>
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<fC03 i1="11" i2="X" l="ENG"><s0>Severe acute respiratory syndrome</s0>
<s2>NM</s2>
<s5>14</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>Síndrome respiratorio agudo severo</s0>
<s2>NM</s2>
<s5>14</s5>
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<fC03 i1="12" i2="X" l="FRE"><s0>Carcinome hépatocellulaire</s0>
<s5>15</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG"><s0>Hepatocellular carcinoma</s0>
<s5>15</s5>
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<fC03 i1="12" i2="X" l="SPA"><s0>Carcinoma hepatocelular</s0>
<s5>15</s5>
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<s5>67</s5>
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<fC03 i1="13" i2="X" l="ENG"><s0>Virology</s0>
<s5>67</s5>
</fC03>
<fC03 i1="13" i2="X" l="SPA"><s0>Virología</s0>
<s5>67</s5>
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<fC07 i1="01" i2="X" l="FRE"><s0>Coronaviridae</s0>
<s2>NW</s2>
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<s2>NW</s2>
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<s2>NW</s2>
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<s2>NW</s2>
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<s2>NW</s2>
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<s2>NW</s2>
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<s2>NW</s2>
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<s2>NW</s2>
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<fC07 i1="03" i2="X" l="SPA"><s0>Virus</s0>
<s2>NW</s2>
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<s2>NM</s2>
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<s2>NM</s2>
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<s2>NM</s2>
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<s5>19</s5>
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<fC07 i1="05" i2="X" l="ENG"><s0>Respiratory disease</s0>
<s5>19</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Aparato respiratorio patología</s0>
<s5>19</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Poumon pathologie</s0>
<s5>20</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Lung disease</s0>
<s5>20</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Pulmón patología</s0>
<s5>20</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Appareil digestif pathologie</s0>
<s5>22</s5>
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<s5>22</s5>
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<s5>22</s5>
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<s5>23</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>Hepatic disease</s0>
<s5>23</s5>
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<fC07 i1="08" i2="X" l="SPA"><s0>Hígado patología</s0>
<s5>23</s5>
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<fC07 i1="09" i2="X" l="FRE"><s0>Tumeur maligne</s0>
<s5>24</s5>
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<s5>24</s5>
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<fN21><s1>187</s1>
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<server><NO>PASCAL 04-0316775 INIST</NO>
<ET>S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients</ET>
<AU>HOFMANN (Heike); HATTERMANN (Kim); MARZI (Andrea); GRAMBERG (Thomas); GEIER (Martina); KRUMBIEGEL (Mandy); KUATE (Seraphin); ÜBERLA (Klaus); NIEDRIG (Matthias); PÖHLMANN (Stefan)</AU>
<AF>Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg/91054 Erlangen/Allemagne (1 aut., 3 aut., 4 aut., 5 aut., 6 aut., 10 aut.); Nikolaus-Fiebiger-Center, University Erlangen-Nürnberg/91054 Erlangen/Allemagne (1 aut., 3 aut., 4 aut., 5 aut., 6 aut., 10 aut.); Robert Koch Institute/13353 Berlin/Allemagne (2 aut., 9 aut.); Department for Molecular and Medical Virology, Ruhr University Bochum/44801 Bochum/Allemagne (7 aut., 8 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2004; Vol. 78; No. 12; Pp. 6134-6142; Bibl. 75 ref.</SO>
<LA>Anglais</LA>
<EA>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.</EA>
<CC>002A05C10; 002B04</CC>
<FD>Coronavirus; Homme; Vitronectine; Protéine; Lignée cellulaire; Cellule cible; Anticorps neutralisant; Neutralisation; Infection; Microbiologie; Syndrome respiratoire aigu sévère; Carcinome hépatocellulaire; Virologie</FD>
<FG>Coronaviridae; Nidovirales; Virus; Virose; Appareil respiratoire pathologie; Poumon pathologie; Appareil digestif pathologie; Foie pathologie; Tumeur maligne</FG>
<ED>Coronavirus; Human; Vitronectin; Protein; Cell line; Target cell; Neutralizing antibody; Neutralization; Infection; Microbiology; Severe acute respiratory syndrome; Hepatocellular carcinoma; Virology</ED>
<EG>Coronaviridae; Nidovirales; Virus; Viral disease; Respiratory disease; Lung disease; Digestive diseases; Hepatic disease; Malignant tumor</EG>
<SD>Coronavirus; Hombre; Vitronectina; Proteína; Línea celular; Célula blanco; anticuerpo neutralizante; Neutralización; Infección; Microbiología; Síndrome respiratorio agudo severo; Carcinoma hepatocelular; Virología</SD>
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