Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge
Identifieur interne : 000043 ( PascalFrancis/Checkpoint ); précédent : 000042; suivant : 000044Primary 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
- Pascal (Inist)
English descriptors
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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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></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">12-0189661</idno><date when="2012">2012</date><idno type="stanalyst">PASCAL 12-0189661 INIST</idno><idno type="RBID">Pascal:12-0189661</idno><idno type="wicri:Area/PascalFrancis/Corpus">000067</idno><idno type="wicri:Area/PascalFrancis/Curation">000920</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000043</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000043</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge</title><author><name sortKey="Clay, Candice" sort="Clay, Candice" uniqKey="Clay C" first="Candice" last="Clay">Candice Clay</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="Donart, Nathan" sort="Donart, Nathan" uniqKey="Donart N" first="Nathan" last="Donart">Nathan Donart</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="Fomukong, Ndingsa" sort="Fomukong, Ndingsa" uniqKey="Fomukong N" first="Ndingsa" last="Fomukong">Ndingsa Fomukong</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="Knight, Jennifer B" sort="Knight, Jennifer B" uniqKey="Knight J" first="Jennifer B." last="Knight">Jennifer B. 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>Coronavirus</term><term>Inflammation</term><term>Lung</term><term>Replication</term><term>Severe acute respiratory syndrome</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term><term>Réplication</term><term>Poumon</term><term>Inflammation</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><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>86</s2></fA05><fA06><s2>8</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge</s1></fA08><fA11 i1="01" i2="1"><s1>CLAY (Candice)</s1></fA11><fA11 i1="02" i2="1"><s1>DONART (Nathan)</s1></fA11><fA11 i1="03" i2="1"><s1>FOMUKONG (Ndingsa)</s1></fA11><fA11 i1="04" i2="1"><s1>KNIGHT (Jennifer B.)</s1></fA11><fA11 i1="05" i2="1"><s1>WANLI LEI</s1></fA11><fA11 i1="06" i2="1"><s1>PRICE (Lance)</s1></fA11><fA11 i1="07" i2="1"><s1>HAHN (Fletcher)</s1></fA11><fA11 i1="08" i2="1"><s1>VAN WESTRIENEN (Jesse)</s1></fA11><fA11 i1="09" i2="1"><s1>HARROD (Kevin S.)</s1></fA11><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></fA14><fA20><s1>4234-4244</s1></fA20><fA21><s1>2012</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>13592</s2><s5>354000509696590190</s5></fA43><fA44><s0>0000</s0><s1>© 2012 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>62 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>12-0189661</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>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.</s0></fC01><fC02 i1="01" i2="X"><s0>002A05C10</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>Réplication</s0><s5>05</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Replication</s0><s5>05</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Replicación</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Poumon</s0><s5>06</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Lung</s0><s5>06</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Pulmón</s0><s5>06</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Inflammation</s0><s5>07</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Inflammation</s0><s5>07</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Inflamación</s0><s5>07</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Syndrome respiratoire aigu sévère</s0><s2>NM</s2><s5>14</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Severe acute respiratory syndrome</s0><s2>NM</s2><s5>14</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Síndrome respiratorio agudo severo</s0><s2>NM</s2><s5>14</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Pathologie de l'appareil respiratoire</s0><s5>13</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Respiratory disease</s0><s5>13</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Aparato respiratorio patología</s0><s5>13</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Virose</s0></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Viral disease</s0></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Virosis</s0></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Infection</s0></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Infection</s0></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Infección</s0></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Pathologie des poumons</s0><s5>16</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Lung disease</s0><s5>16</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Pulmón patología</s0><s5>16</s5></fC07><fN21><s1>149</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><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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|texte= Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge
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