Lack of innate interferon responses during SARS coronavirus infection in a vaccination and reinfection ferret model.
Identifieur interne : 001C99 ( Main/Exploration ); précédent : 001C98; suivant : 001D00Lack of innate interferon responses during SARS coronavirus infection in a vaccination and reinfection ferret model.
Auteurs : Mark J. Cameron [Canada] ; Alyson A. Kelvin ; Alberto J. Leon ; Cheryl M. Cameron ; Longsi Ran ; Luoling Xu ; Yong-Kyu Chu ; Ali Danesh ; Yuan Fang ; Qianjun Li ; Austin Anderson ; Ronald C. Couch ; Stephane G. Paquette ; Ndingsa G. Fomukong ; Otfried Kistner ; Manfred Lauchart ; Thomas Rowe ; Kevin S. Harrod ; Colleen B. Jonsson ; David J. KelvinSource :
- PloS one [ 1932-6203 ] ; 2012.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (sang), Cellules Vero, Charge virale, Furets, Immunité innée, Interactions hôte-pathogène, Interférons (génétique), Interférons (métabolisme), Interleukine-6 (génétique), Interleukine-6 (métabolisme), Mâle, Poumon (métabolisme), Poumon (virologie), Protéines du système du complément (génétique), Protéines du système du complément (métabolisme), Régulation de l'expression des gènes, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (métabolisme), Séquençage par oligonucléotides en batterie, Transcriptome, Vaccination, Vaccins antiviraux (administration et posologie), Virus du SRAS (immunologie), Virus du SRAS (physiologie).
- MESH :
- administration et posologie : Vaccins antiviraux.
- génétique : Interférons, Interleukine-6, Protéines du système du complément.
- immunologie : Syndrome respiratoire aigu sévère, Virus du SRAS.
- métabolisme : Interférons, Interleukine-6, Poumon, Protéines du système du complément, Syndrome respiratoire aigu sévère.
- physiologie : Virus du SRAS.
- sang : Anticorps antiviraux.
- virologie : Poumon.
- Animaux, Cellules Vero, Charge virale, Furets, Immunité innée, Interactions hôte-pathogène, Mâle, Régulation de l'expression des gènes, Syndrome respiratoire aigu sévère, Séquençage par oligonucléotides en batterie, Transcriptome, Vaccination.
English descriptors
- KwdEn :
- Animals, Antibodies, Viral (blood), Chlorocebus aethiops, Complement System Proteins (genetics), Complement System Proteins (metabolism), Ferrets, Gene Expression Regulation, Host-Pathogen Interactions, Immunity, Innate, Interferons (genetics), Interferons (metabolism), Interleukin-6 (genetics), Interleukin-6 (metabolism), Lung (metabolism), Lung (virology), Male, Oligonucleotide Array Sequence Analysis, SARS Virus (immunology), SARS Virus (physiology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (metabolism), Severe Acute Respiratory Syndrome (prevention & control), Transcriptome, Vaccination, Vero Cells, Viral Load, Viral Vaccines (administration & dosage).
- MESH :
- chemical , administration & dosage : Viral Vaccines.
- chemical , blood : Antibodies, Viral.
- chemical , genetics : Complement System Proteins, Interferons, Interleukin-6.
- chemical , metabolism : Complement System Proteins, Interferons, Interleukin-6.
- immunology : SARS Virus, Severe Acute Respiratory Syndrome.
- metabolism : Lung, Severe Acute Respiratory Syndrome.
- physiology : SARS Virus.
- prevention & control : Severe Acute Respiratory Syndrome.
- virology : Lung.
- Animals, Chlorocebus aethiops, Ferrets, Gene Expression Regulation, Host-Pathogen Interactions, Immunity, Innate, Male, Oligonucleotide Array Sequence Analysis, Transcriptome, Vaccination, Vero Cells, Viral Load.
Abstract
In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)(3)-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.
DOI: 10.1371/journal.pone.0045842
PubMed: 23029269
Affiliations:
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Kelvin</name></author><author><name sortKey="Leon, Alberto J" sort="Leon, Alberto J" uniqKey="Leon A" first="Alberto J" last="Leon">Alberto J. Leon</name></author><author><name sortKey="Cameron, Cheryl M" sort="Cameron, Cheryl M" uniqKey="Cameron C" first="Cheryl M" last="Cameron">Cheryl M. 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Cameron</name><affiliation wicri:level="1"><nlm:affiliation>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Kelvin, Alyson A" sort="Kelvin, Alyson A" uniqKey="Kelvin A" first="Alyson A" last="Kelvin">Alyson A. Kelvin</name></author><author><name sortKey="Leon, Alberto J" sort="Leon, Alberto J" uniqKey="Leon A" first="Alberto J" last="Leon">Alberto J. Leon</name></author><author><name sortKey="Cameron, Cheryl M" sort="Cameron, Cheryl M" uniqKey="Cameron C" first="Cheryl M" last="Cameron">Cheryl M. Cameron</name></author><author><name sortKey="Ran, Longsi" sort="Ran, Longsi" uniqKey="Ran L" first="Longsi" last="Ran">Longsi Ran</name></author><author><name sortKey="Xu, Luoling" sort="Xu, Luoling" uniqKey="Xu L" first="Luoling" last="Xu">Luoling Xu</name></author><author><name sortKey="Chu, Yong Kyu" sort="Chu, Yong Kyu" uniqKey="Chu Y" first="Yong-Kyu" last="Chu">Yong-Kyu Chu</name></author><author><name sortKey="Danesh, Ali" sort="Danesh, Ali" uniqKey="Danesh A" first="Ali" last="Danesh">Ali Danesh</name></author><author><name sortKey="Fang, Yuan" sort="Fang, Yuan" uniqKey="Fang Y" first="Yuan" last="Fang">Yuan Fang</name></author><author><name sortKey="Li, Qianjun" sort="Li, Qianjun" uniqKey="Li Q" first="Qianjun" last="Li">Qianjun Li</name></author><author><name sortKey="Anderson, Austin" sort="Anderson, Austin" uniqKey="Anderson A" first="Austin" last="Anderson">Austin Anderson</name></author><author><name sortKey="Couch, Ronald C" sort="Couch, Ronald C" uniqKey="Couch R" first="Ronald C" last="Couch">Ronald C. Couch</name></author><author><name sortKey="Paquette, Stephane G" sort="Paquette, Stephane G" uniqKey="Paquette S" first="Stephane G" last="Paquette">Stephane G. Paquette</name></author><author><name sortKey="Fomukong, Ndingsa G" sort="Fomukong, Ndingsa G" uniqKey="Fomukong N" first="Ndingsa G" last="Fomukong">Ndingsa G. Fomukong</name></author><author><name sortKey="Kistner, Otfried" sort="Kistner, Otfried" uniqKey="Kistner O" first="Otfried" last="Kistner">Otfried Kistner</name></author><author><name sortKey="Lauchart, Manfred" sort="Lauchart, Manfred" uniqKey="Lauchart M" first="Manfred" last="Lauchart">Manfred Lauchart</name></author><author><name sortKey="Rowe, Thomas" sort="Rowe, Thomas" uniqKey="Rowe T" first="Thomas" last="Rowe">Thomas Rowe</name></author><author><name sortKey="Harrod, Kevin S" sort="Harrod, Kevin S" uniqKey="Harrod K" first="Kevin S" last="Harrod">Kevin S. Harrod</name></author><author><name sortKey="Jonsson, Colleen B" sort="Jonsson, Colleen B" uniqKey="Jonsson C" first="Colleen B" last="Jonsson">Colleen B. Jonsson</name></author><author><name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J" last="Kelvin">David J. Kelvin</name></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Viral (blood)</term><term>Chlorocebus aethiops</term><term>Complement System Proteins (genetics)</term><term>Complement System Proteins (metabolism)</term><term>Ferrets</term><term>Gene Expression Regulation</term><term>Host-Pathogen Interactions</term><term>Immunity, Innate</term><term>Interferons (genetics)</term><term>Interferons (metabolism)</term><term>Interleukin-6 (genetics)</term><term>Interleukin-6 (metabolism)</term><term>Lung (metabolism)</term><term>Lung (virology)</term><term>Male</term><term>Oligonucleotide Array Sequence Analysis</term><term>SARS Virus (immunology)</term><term>SARS Virus (physiology)</term><term>Severe Acute Respiratory Syndrome (immunology)</term><term>Severe Acute Respiratory Syndrome (metabolism)</term><term>Severe Acute Respiratory Syndrome (prevention & control)</term><term>Transcriptome</term><term>Vaccination</term><term>Vero Cells</term><term>Viral Load</term><term>Viral Vaccines (administration & dosage)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antiviraux (sang)</term><term>Cellules Vero</term><term>Charge virale</term><term>Furets</term><term>Immunité innée</term><term>Interactions hôte-pathogène</term><term>Interférons (génétique)</term><term>Interférons (métabolisme)</term><term>Interleukine-6 (génétique)</term><term>Interleukine-6 (métabolisme)</term><term>Mâle</term><term>Poumon (métabolisme)</term><term>Poumon (virologie)</term><term>Protéines du système du complément (génétique)</term><term>Protéines du système du complément (métabolisme)</term><term>Régulation de l'expression des gènes</term><term>Syndrome respiratoire aigu sévère ()</term><term>Syndrome respiratoire aigu sévère (immunologie)</term><term>Syndrome respiratoire aigu sévère (métabolisme)</term><term>Séquençage par oligonucléotides en batterie</term><term>Transcriptome</term><term>Vaccination</term><term>Vaccins antiviraux (administration et posologie)</term><term>Virus du SRAS (immunologie)</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Viral Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Complement System Proteins</term><term>Interferons</term><term>Interleukin-6</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Complement System Proteins</term><term>Interferons</term><term>Interleukin-6</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Vaccins antiviraux</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Interférons</term><term>Interleukine-6</term><term>Protéines du système du complément</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>SARS Virus</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Interférons</term><term>Interleukine-6</term><term>Poumon</term><term>Protéines du système du complément</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Anticorps antiviraux</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Ferrets</term><term>Gene Expression Regulation</term><term>Host-Pathogen Interactions</term><term>Immunity, Innate</term><term>Male</term><term>Oligonucleotide Array Sequence Analysis</term><term>Transcriptome</term><term>Vaccination</term><term>Vero Cells</term><term>Viral Load</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Charge virale</term><term>Furets</term><term>Immunité innée</term><term>Interactions hôte-pathogène</term><term>Mâle</term><term>Régulation de l'expression des gènes</term><term>Syndrome respiratoire aigu sévère</term><term>Séquençage par oligonucléotides en batterie</term><term>Transcriptome</term><term>Vaccination</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)(3)-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Anderson, Austin" sort="Anderson, Austin" uniqKey="Anderson A" first="Austin" last="Anderson">Austin Anderson</name><name sortKey="Cameron, Cheryl M" sort="Cameron, Cheryl M" uniqKey="Cameron C" first="Cheryl M" last="Cameron">Cheryl M. Cameron</name><name sortKey="Chu, Yong Kyu" sort="Chu, Yong Kyu" uniqKey="Chu Y" first="Yong-Kyu" last="Chu">Yong-Kyu Chu</name><name sortKey="Couch, Ronald C" sort="Couch, Ronald C" uniqKey="Couch R" first="Ronald C" last="Couch">Ronald C. Couch</name><name sortKey="Danesh, Ali" sort="Danesh, Ali" uniqKey="Danesh A" first="Ali" last="Danesh">Ali Danesh</name><name sortKey="Fang, Yuan" sort="Fang, Yuan" uniqKey="Fang Y" first="Yuan" last="Fang">Yuan Fang</name><name sortKey="Fomukong, Ndingsa G" sort="Fomukong, Ndingsa G" uniqKey="Fomukong N" first="Ndingsa G" last="Fomukong">Ndingsa G. Fomukong</name><name sortKey="Harrod, Kevin S" sort="Harrod, Kevin S" uniqKey="Harrod K" first="Kevin S" last="Harrod">Kevin S. Harrod</name><name sortKey="Jonsson, Colleen B" sort="Jonsson, Colleen B" uniqKey="Jonsson C" first="Colleen B" last="Jonsson">Colleen B. Jonsson</name><name sortKey="Kelvin, Alyson A" sort="Kelvin, Alyson A" uniqKey="Kelvin A" first="Alyson A" last="Kelvin">Alyson A. Kelvin</name><name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J" last="Kelvin">David J. Kelvin</name><name sortKey="Kistner, Otfried" sort="Kistner, Otfried" uniqKey="Kistner O" first="Otfried" last="Kistner">Otfried Kistner</name><name sortKey="Lauchart, Manfred" sort="Lauchart, Manfred" uniqKey="Lauchart M" first="Manfred" last="Lauchart">Manfred Lauchart</name><name sortKey="Leon, Alberto J" sort="Leon, Alberto J" uniqKey="Leon A" first="Alberto J" last="Leon">Alberto J. Leon</name><name sortKey="Li, Qianjun" sort="Li, Qianjun" uniqKey="Li Q" first="Qianjun" last="Li">Qianjun Li</name><name sortKey="Paquette, Stephane G" sort="Paquette, Stephane G" uniqKey="Paquette S" first="Stephane G" last="Paquette">Stephane G. Paquette</name><name sortKey="Ran, Longsi" sort="Ran, Longsi" uniqKey="Ran L" first="Longsi" last="Ran">Longsi Ran</name><name sortKey="Rowe, Thomas" sort="Rowe, Thomas" uniqKey="Rowe T" first="Thomas" last="Rowe">Thomas Rowe</name><name sortKey="Xu, Luoling" sort="Xu, Luoling" uniqKey="Xu L" first="Luoling" last="Xu">Luoling Xu</name></noCountry><country name="Canada"><noRegion><name sortKey="Cameron, Mark J" sort="Cameron, Mark J" uniqKey="Cameron M" first="Mark J" last="Cameron">Mark J. Cameron</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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