Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge
Identifieur interne : 001F70 ( Main/Exploration ); précédent : 001F69; suivant : 001F71Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge
Auteurs : Candice Clay [États-Unis] ; Nathan Donart [États-Unis] ; Ndingsa Fomukong [États-Unis] ; Jennifer B. Knight [États-Unis] ; WANLI LEI [États-Unis] ; Lance Price [États-Unis] ; Fletcher Hahn [États-Unis] ; Jesse Van Westrienen [États-Unis] ; Kevin S. Harrod [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2012.
Descripteurs français
- KwdFr :
- Activation des macrophages (immunologie), Animaux, Anticorps antiviraux (immunologie), Cellules dendritiques (immunologie), Coronavirus (immunologie), Cytokines (métabolisme), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (immunologie), Humains, Immunoglobuline A (immunologie), Immunoglobuline G (immunologie), Lignée cellulaire, Lymphocytes T (immunologie), Macrophages (immunologie), Monocytes (immunologie), Pneumopathie infectieuse (anatomopathologie), Pneumopathie infectieuse (immunologie), Pneumopathie infectieuse (virologie), Poumon (anatomopathologie), Poumon (immunologie), Poumon (virologie), Protéines de l'enveloppe virale (immunologie), Réplication virale, Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (métabolisme), Syndrome respiratoire aigu sévère (virologie).
- MESH :
- anatomopathologie : Pneumopathie infectieuse, Poumon.
- immunologie : Activation des macrophages, Anticorps antiviraux, Cellules dendritiques, Coronavirus, Glycoprotéines membranaires, Immunoglobuline A, Immunoglobuline G, Lymphocytes T, Macrophages, Monocytes, Pneumopathie infectieuse, Poumon, Protéines de l'enveloppe virale, Syndrome respiratoire aigu sévère.
- métabolisme : Cytokines, Syndrome respiratoire aigu sévère.
- virologie : Pneumopathie infectieuse, Poumon, Syndrome respiratoire aigu sévère.
- Pascal (Inist)
English descriptors
- KwdEn :
- Animals, Antibodies, Viral (immunology), Cell Line, Chlorocebus aethiops, Coronavirus, Coronavirus (immunology), Cytokines (metabolism), Dendritic Cells (immunology), Humans, Immunoglobulin A (immunology), Immunoglobulin G (immunology), Inflammation, Lung, Lung (immunology), Lung (pathology), Lung (virology), Macrophage Activation (immunology), Macrophages (immunology), Membrane Glycoproteins (immunology), Monocytes (immunology), Pneumonia (immunology), Pneumonia (pathology), Pneumonia (virology), Replication, Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (metabolism), Severe Acute Respiratory Syndrome (virology), Severe acute respiratory syndrome, Spike Glycoprotein, Coronavirus, T-Lymphocytes (immunology), Viral Envelope Proteins (immunology), Virus Replication.
- MESH :
- chemical , immunology : Antibodies, Viral, Immunoglobulin A, Immunoglobulin G, Membrane Glycoproteins, Viral Envelope Proteins.
- immunology : Coronavirus, Dendritic Cells, Lung, Macrophage Activation, Macrophages, Monocytes, Pneumonia, Severe Acute Respiratory Syndrome, T-Lymphocytes.
- chemical , metabolism : Cytokines, Severe Acute Respiratory Syndrome.
- pathology : Lung, Pneumonia.
- virology : Lung, Pneumonia, Severe Acute Respiratory Syndrome.
- Animals, Cell Line, Chlorocebus aethiops, Humans, Spike Glycoprotein, Coronavirus, Virus Replication.
Abstract
Our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (SARS-CoV) infection is limited, and little is known about the dynamics of the immune response at the primary site of disease. Here, an African green monkey (AGM) model was used to elucidate immune mechanisms that facilitate viral clearance but may also contribute to persistent lung inflammation following SARS-CoV infection. During primary infection, SARS-CoV replicated in the AGM lung for up to 10 days. Interestingly, lung inflammation was more prevalent following viral clearance, as leukocyte numbers peaked at 14 days postinfection (dpi) and remained elevated at 28 dpi compared to those of mock-infected controls. Lung macrophages but not dendritic cells were rapidly activated, and both cell types had high activation marker expression at late infection time points. Lung proinflammatory cytokines were induced at 1 to 14 dpi, but most returned to baseline by 28 dpi except interleukin 12 (IL-12) and gamma interferon. In SARS-CoV homologous rechallenge studies, 11 of the 12 animals were free of replicating virus at day 5 after rechallenge. However, incidence and severity of lung inflammation was not reduced despite the limited viral replication upon rechallenge. Evaluating the role of antibodies in immune protection or potentiation revealed a progressive increase in anti-SARS-CoV antibodies in lung and serum that did not correlate temporally or spatially with enhanced viral replication. This study represents one of the first comprehensive analyses of lung immunity, including changes in leukocyte populations, lung-specific cytokines, and antibody responses following SARS-CoV rechallenge in AGMs.
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Le document en format XML
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Knight</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Lovelace Respiratory Research Institute, Infectious Disease Program</s1><s2>Albuquerque, New Mexico</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Nouveau-Mexique</region></placeName></affiliation></author><author><name sortKey="Wanli Lei" sort="Wanli Lei" uniqKey="Wanli Lei" last="Wanli Lei">WANLI LEI</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Lovelace Respiratory Research Institute, Infectious Disease Program</s1><s2>Albuquerque, New Mexico</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Nouveau-Mexique</region></placeName></affiliation></author><author><name sortKey="Price, Lance" sort="Price, Lance" uniqKey="Price L" first="Lance" last="Price">Lance Price</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Lovelace Respiratory Research Institute, Infectious Disease Program</s1><s2>Albuquerque, New Mexico</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Nouveau-Mexique</region></placeName></affiliation></author><author><name sortKey="Hahn, Fletcher" sort="Hahn, Fletcher" uniqKey="Hahn F" first="Fletcher" last="Hahn">Fletcher Hahn</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Lovelace Respiratory Research Institute, Infectious Disease Program</s1><s2>Albuquerque, New Mexico</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Nouveau-Mexique</region></placeName></affiliation></author><author><name sortKey="Van Westrienen, Jesse" sort="Van Westrienen, Jesse" uniqKey="Van Westrienen J" first="Jesse" last="Van Westrienen">Jesse Van Westrienen</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Lovelace Respiratory Research Institute, Infectious Disease Program</s1><s2>Albuquerque, New Mexico</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Nouveau-Mexique</region></placeName></affiliation></author><author><name sortKey="Harrod, Kevin S" sort="Harrod, Kevin S" uniqKey="Harrod K" first="Kevin S." last="Harrod">Kevin S. Harrod</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Lovelace Respiratory Research Institute, Infectious Disease Program</s1><s2>Albuquerque, New Mexico</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Nouveau-Mexique</region></placeName></affiliation></author></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="2012">2012</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><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Viral (immunology)</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Coronavirus</term><term>Coronavirus (immunology)</term><term>Cytokines (metabolism)</term><term>Dendritic Cells (immunology)</term><term>Humans</term><term>Immunoglobulin A (immunology)</term><term>Immunoglobulin G (immunology)</term><term>Inflammation</term><term>Lung</term><term>Lung (immunology)</term><term>Lung (pathology)</term><term>Lung (virology)</term><term>Macrophage Activation (immunology)</term><term>Macrophages (immunology)</term><term>Membrane Glycoproteins (immunology)</term><term>Monocytes (immunology)</term><term>Pneumonia (immunology)</term><term>Pneumonia (pathology)</term><term>Pneumonia (virology)</term><term>Replication</term><term>Severe Acute Respiratory Syndrome (immunology)</term><term>Severe Acute Respiratory Syndrome (metabolism)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Severe acute respiratory syndrome</term><term>Spike Glycoprotein, Coronavirus</term><term>T-Lymphocytes (immunology)</term><term>Viral Envelope Proteins (immunology)</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation des macrophages (immunologie)</term><term>Animaux</term><term>Anticorps antiviraux (immunologie)</term><term>Cellules dendritiques (immunologie)</term><term>Coronavirus (immunologie)</term><term>Cytokines (métabolisme)</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (immunologie)</term><term>Humains</term><term>Immunoglobuline A (immunologie)</term><term>Immunoglobuline G (immunologie)</term><term>Lignée cellulaire</term><term>Lymphocytes T (immunologie)</term><term>Macrophages (immunologie)</term><term>Monocytes (immunologie)</term><term>Pneumopathie infectieuse (anatomopathologie)</term><term>Pneumopathie infectieuse (immunologie)</term><term>Pneumopathie infectieuse (virologie)</term><term>Poumon (anatomopathologie)</term><term>Poumon (immunologie)</term><term>Poumon (virologie)</term><term>Protéines de l'enveloppe virale (immunologie)</term><term>Réplication virale</term><term>Syndrome respiratoire aigu sévère (immunologie)</term><term>Syndrome respiratoire aigu sévère (métabolisme)</term><term>Syndrome respiratoire aigu sévère (virologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Viral</term><term>Immunoglobulin A</term><term>Immunoglobulin G</term><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Pneumopathie infectieuse</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Activation des macrophages</term><term>Anticorps antiviraux</term><term>Cellules dendritiques</term><term>Coronavirus</term><term>Glycoprotéines membranaires</term><term>Immunoglobuline A</term><term>Immunoglobuline G</term><term>Lymphocytes T</term><term>Macrophages</term><term>Monocytes</term><term>Pneumopathie infectieuse</term><term>Poumon</term><term>Protéines de l'enveloppe virale</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus</term><term>Dendritic Cells</term><term>Lung</term><term>Macrophage Activation</term><term>Macrophages</term><term>Monocytes</term><term>Pneumonia</term><term>Severe Acute Respiratory Syndrome</term><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cytokines</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cytokines</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term><term>Pneumonia</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Pneumopathie infectieuse</term><term>Poumon</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung</term><term>Pneumonia</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Humans</term><term>Spike Glycoprotein, Coronavirus</term><term>Virus Replication</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term><term>Coronavirus</term><term>Glycoprotéine de spicule des coronavirus</term><term>Humains</term><term>Lignée cellulaire</term><term>Réplication</term><term>Poumon</term><term>Inflammation</term><term>Réplication virale</term><term>Syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (SARS-CoV) infection is limited, and little is known about the dynamics of the immune response at the primary site of disease. Here, an African green monkey (AGM) model was used to elucidate immune mechanisms that facilitate viral clearance but may also contribute to persistent lung inflammation following SARS-CoV infection. During primary infection, SARS-CoV replicated in the AGM lung for up to 10 days. Interestingly, lung inflammation was more prevalent following viral clearance, as leukocyte numbers peaked at 14 days postinfection (dpi) and remained elevated at 28 dpi compared to those of mock-infected controls. Lung macrophages but not dendritic cells were rapidly activated, and both cell types had high activation marker expression at late infection time points. Lung proinflammatory cytokines were induced at 1 to 14 dpi, but most returned to baseline by 28 dpi except interleukin 12 (IL-12) and gamma interferon. In SARS-CoV homologous rechallenge studies, 11 of the 12 animals were free of replicating virus at day 5 after rechallenge. However, incidence and severity of lung inflammation was not reduced despite the limited viral replication upon rechallenge. Evaluating the role of antibodies in immune protection or potentiation revealed a progressive increase in anti-SARS-CoV antibodies in lung and serum that did not correlate temporally or spatially with enhanced viral replication. This study represents one of the first comprehensive analyses of lung immunity, including changes in leukocyte populations, lung-specific cytokines, and antibody responses following SARS-CoV rechallenge in AGMs.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Nouveau-Mexique</li></region></list><tree><country name="États-Unis"><region name="Nouveau-Mexique"><name sortKey="Clay, Candice" sort="Clay, Candice" uniqKey="Clay C" first="Candice" last="Clay">Candice Clay</name></region><name sortKey="Donart, Nathan" sort="Donart, Nathan" uniqKey="Donart N" first="Nathan" last="Donart">Nathan Donart</name><name sortKey="Fomukong, Ndingsa" sort="Fomukong, Ndingsa" uniqKey="Fomukong N" first="Ndingsa" last="Fomukong">Ndingsa Fomukong</name><name sortKey="Hahn, Fletcher" sort="Hahn, Fletcher" uniqKey="Hahn F" first="Fletcher" last="Hahn">Fletcher Hahn</name><name sortKey="Harrod, Kevin S" sort="Harrod, Kevin S" uniqKey="Harrod K" first="Kevin S." last="Harrod">Kevin S. Harrod</name><name sortKey="Knight, Jennifer B" sort="Knight, Jennifer B" uniqKey="Knight J" first="Jennifer B." last="Knight">Jennifer B. Knight</name><name sortKey="Price, Lance" sort="Price, Lance" uniqKey="Price L" first="Lance" last="Price">Lance Price</name><name sortKey="Van Westrienen, Jesse" sort="Van Westrienen, Jesse" uniqKey="Van Westrienen J" first="Jesse" last="Van Westrienen">Jesse Van Westrienen</name><name sortKey="Wanli Lei" sort="Wanli Lei" uniqKey="Wanli Lei" last="Wanli Lei">WANLI LEI</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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