SARS-CoV replication and pathogenesis in an in vitro model of the human conducting airway epithelium
Identifieur interne : 003601 ( Main/Exploration ); précédent : 003600; suivant : 003602SARS-CoV replication and pathogenesis in an in vitro model of the human conducting airway epithelium
Auteurs : Amy C. Sims [États-Unis] ; Susan E. Burkett [États-Unis] ; Boyd Yount [États-Unis] ; Raymond J. Pickles [États-Unis]Source :
- Virus Research [ 0168-1702 ] ; 2007.
Descripteurs français
- KwdFr :
- Animaux, Appareil respiratoire (virologie), Cellules Caco-2, Cellules Vero, Cellules cultivées, Cellules épithéliales (virologie), Cricetinae, Humains, Lignée cellulaire, Macaca mulatta, Mesocricetus, Peptidyl-Dipeptidase A (métabolisme), Poumon (virologie), Pénétration virale, Réplication virale, Souris, Syndrome respiratoire aigu sévère (virologie), Virus du SRAS (croissance et développement), Virus du SRAS (physiologie).
- MESH :
- croissance et développement : Virus du SRAS.
- métabolisme : Peptidyl-Dipeptidase A.
- physiologie : Virus du SRAS.
- virologie : Appareil respiratoire, Cellules épithéliales, Poumon, Syndrome respiratoire aigu sévère.
- Animaux, Cellules Caco-2, Cellules Vero, Cellules cultivées, Cricetinae, Humains, Lignée cellulaire, Macaca mulatta, Mesocricetus, Pénétration virale, Réplication virale, Souris.
English descriptors
- KwdEn :
- Animals, Caco-2 Cells, Cell Line, Cells, Cultured, Chlorocebus aethiops, Cricetinae, Epithelial Cells (virology), Humans, Lung (virology), Macaca mulatta, Mesocricetus, Mice, Peptidyl-Dipeptidase A (metabolism), Respiratory System (virology), SARS Virus (growth & development), SARS Virus (physiology), Severe Acute Respiratory Syndrome (virology), Vero Cells, Virus Internalization, Virus Replication.
- MESH :
- chemical , metabolism : Peptidyl-Dipeptidase A.
- growth & development : SARS Virus.
- physiology : SARS Virus.
- virology : Epithelial Cells, Lung, Respiratory System, Severe Acute Respiratory Syndrome.
- Animals, Caco-2 Cells, Cell Line, Cells, Cultured, Chlorocebus aethiops, Cricetinae, Humans, Macaca mulatta, Mesocricetus, Mice, Vero Cells, Virus Internalization, Virus Replication.
Abstract
SARS coronavirus (SARS-CoV) emerged in 2002 as an important cause of severe lower respiratory tract infection in humans and
Url:
DOI: 10.1016/j.virusres.2007.03.013
PubMed: 17451829
PubMed Central: 2384224
Affiliations:
- États-Unis
- Caroline du Nord
- Chapel Hill (Caroline du Nord)
- Université de Caroline du Nord à Chapel Hill
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Le document en format XML
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<series><title level="j">Virus Research</title>
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<term>Caco-2 Cells</term>
<term>Cell Line</term>
<term>Cells, Cultured</term>
<term>Chlorocebus aethiops</term>
<term>Cricetinae</term>
<term>Epithelial Cells (virology)</term>
<term>Humans</term>
<term>Lung (virology)</term>
<term>Macaca mulatta</term>
<term>Mesocricetus</term>
<term>Mice</term>
<term>Peptidyl-Dipeptidase A (metabolism)</term>
<term>Respiratory System (virology)</term>
<term>SARS Virus (growth & development)</term>
<term>SARS Virus (physiology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Vero Cells</term>
<term>Virus Internalization</term>
<term>Virus Replication</term>
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<term>Appareil respiratoire (virologie)</term>
<term>Cellules Caco-2</term>
<term>Cellules Vero</term>
<term>Cellules cultivées</term>
<term>Cellules épithéliales (virologie)</term>
<term>Cricetinae</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Macaca mulatta</term>
<term>Mesocricetus</term>
<term>Peptidyl-Dipeptidase A (métabolisme)</term>
<term>Poumon (virologie)</term>
<term>Pénétration virale</term>
<term>Réplication virale</term>
<term>Souris</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Virus du SRAS (croissance et développement)</term>
<term>Virus du SRAS (physiologie)</term>
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<keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>SARS Virus</term>
</keywords>
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<term>Poumon</term>
<term>Syndrome respiratoire aigu sévère</term>
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<term>Severe Acute Respiratory Syndrome</term>
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<term>Caco-2 Cells</term>
<term>Cell Line</term>
<term>Cells, Cultured</term>
<term>Chlorocebus aethiops</term>
<term>Cricetinae</term>
<term>Humans</term>
<term>Macaca mulatta</term>
<term>Mesocricetus</term>
<term>Mice</term>
<term>Vero Cells</term>
<term>Virus Internalization</term>
<term>Virus Replication</term>
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<term>Cellules Vero</term>
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<term>Lignée cellulaire</term>
<term>Macaca mulatta</term>
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<front><div type="abstract" xml:lang="en"><p>SARS coronavirus (SARS-CoV) emerged in 2002 as an important cause of severe lower respiratory tract infection in humans and <italic>in vitro</italic>
models of the lung are needed to elucidate cellular targets and the consequences of viral infection. The severe and sudden onset of symptoms, resulting in an atypical pneumonia with dry cough and persistent high fever in cases of severe acute respiratory virus brought to light the importance of coronaviruses as potentially lethal human pathogens and the identification of several zoonotic reservoirs has made the reemergence of new strains and future epidemics all the more possible. In this chapter, we describe the pathology of SARS-CoV infection in humans and explore the use of two models of the human conducting airway to develop a better understanding of the replication and pathogenesis of SARS-CoV in relevant <italic>in vitro</italic>
systems. The first culture model is a human bronchial epithelial cell line Calu-3 that can be inoculated by viruses either as a non-polarized monolayer of cells or polarized cells with tight junctions and microvilli. The second model system, derived from primary cells isolated from human airway epithelium and grown on Transwells, form a pseudostratified mucociliary epithelium that recapitulates the morphological and physiological features of the human conducting airway <italic>in vivo</italic>
. Experimental results using these lung epithelial cell models demonstrate that in contrast to the pathology reported in late stage cases SARS-CoV replicates to high titers in epithelial cells of the conducting airway. The SARS-CoV receptor, human angiotensin 1 converting enzyme 2 (hACE2), was detected exclusively on the apical surface of cells in polarized Calu-3 cells and human airway epithelial cultures (HAE), indicating that hACE2 was accessible by SARS-CoV after lumenal airway delivery. Furthermore, in HAE, hACE2 was exclusively localized to ciliated airway epithelial cells. In support of the hACE2 localization data, the most productive route of inoculation and progeny virion egress in both polarized Calu-3 and ciliated cells of HAE was the apical surface suggesting mechanisms to release large quantities of virus into the lumen of the human lung. Preincubation of the apical surface of cultures with antisera directed against hACE2 reduced viral titers by two logs while antisera against DC-SIGN/DC-SIGNR did not reduce viral replication levels suggesting that hACE2 is the primary receptor for entry of SARS-CoV into the ciliated cells of HAE cultures. To assess infectivity in ciliated airway cultures derived from susceptible animal species we generated a recombinant SARS-CoV by deletion of open reading frame 7a/7b (ORF 7a/7b) and insertion of the green fluorescent protein (GFP) resulting in SARS-CoV GFP. SARS-CoV GFP replicated to similar titers as wild type viruses in Vero E6, MA104, and CaCo2 cells. In addition, SARS-CoV replication in airway epithelial cultures generated from Golden Syrian hamster tracheas reached similar titers to the human cultures by 72 h post-infection. Efficient SARS-CoV infection of ciliated cell-types in HAE provides a useful <italic>in vitro</italic>
model of human lung origin to study characteristics of SARS-CoV replication and pathogenesis.</p>
</div>
</front>
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</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
</region>
<settlement><li>Chapel Hill (Caroline du Nord)</li>
</settlement>
<orgName><li>Université de Caroline du Nord à Chapel Hill</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C." last="Sims">Amy C. Sims</name>
</region>
<name sortKey="Burkett, Susan E" sort="Burkett, Susan E" uniqKey="Burkett S" first="Susan E." last="Burkett">Susan E. Burkett</name>
<name sortKey="Pickles, Raymond J" sort="Pickles, Raymond J" uniqKey="Pickles R" first="Raymond J." last="Pickles">Raymond J. Pickles</name>
<name sortKey="Pickles, Raymond J" sort="Pickles, Raymond J" uniqKey="Pickles R" first="Raymond J." last="Pickles">Raymond J. Pickles</name>
<name sortKey="Yount, Boyd" sort="Yount, Boyd" uniqKey="Yount B" first="Boyd" last="Yount">Boyd Yount</name>
</country>
</tree>
</affiliations>
</record>
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