Tropism of and innate immune responses to the novel human betacoronavirus lineage C virus in human ex vivo respiratory organ cultures.
Identifieur interne : 001823 ( Main/Exploration ); précédent : 001822; suivant : 001824Tropism of and innate immune responses to the novel human betacoronavirus lineage C virus in human ex vivo respiratory organ cultures.
Auteurs : Renee W Y. Chan [République populaire de Chine] ; Michael C W. Chan ; Sudhakar Agnihothram ; Louisa L Y. Chan ; Denise I T. Kuok ; Joanne H M. Fong ; Y. Guan ; Leo L M. Poon ; Ralph S. Baric ; John M. Nicholls ; J S Malik PeirisSource :
- Journal of virology [ 1098-5514 ] ; 2013.
Descripteurs français
- KwdFr :
- Bronches (cytologie), Bronches (virologie), Cellules épithéliales (virologie), Coronavirus (), Coronavirus (génétique), Coronavirus (immunologie), Coronavirus (physiologie), Coronavirus humain 229E (physiologie), Humains, Immunité innée, Infections à coronavirus (immunologie), Infections à coronavirus (virologie), Interférons (pharmacologie), Lignée cellulaire, Poumon (cytologie), Poumon (virologie), Récepteurs viraux (métabolisme), Réplication virale, Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (virologie), Techniques de culture d'organes, Tropisme viral, Virus du SRAS (physiologie).
- MESH :
- cytologie : Bronches, Poumon.
- génétique : Coronavirus.
- immunologie : Coronavirus, Infections à coronavirus, Syndrome respiratoire aigu sévère.
- métabolisme : Récepteurs viraux.
- pharmacologie : Interférons.
- physiologie : Coronavirus, Coronavirus humain 229E, Virus du SRAS.
- virologie : Bronches, Cellules épithéliales, Infections à coronavirus, Poumon, Syndrome respiratoire aigu sévère.
- Coronavirus, Humains, Immunité innée, Lignée cellulaire, Réplication virale, Techniques de culture d'organes, Tropisme viral.
English descriptors
- KwdEn :
- Bronchi (cytology), Bronchi (virology), Cell Line, Coronavirus (drug effects), Coronavirus (genetics), Coronavirus (immunology), Coronavirus (physiology), Coronavirus 229E, Human (physiology), Coronavirus Infections (immunology), Coronavirus Infections (virology), Epithelial Cells (virology), Humans, Immunity, Innate, Interferons (pharmacology), Lung (cytology), Lung (virology), Organ Culture Techniques, Receptors, Virus (metabolism), SARS Virus (physiology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (virology), Viral Tropism, Virus Replication.
- MESH :
- chemical , metabolism : Receptors, Virus.
- chemical , pharmacology : Interferons.
- cytology : Bronchi, Lung.
- drug effects : Coronavirus.
- genetics : Coronavirus.
- immunology : Coronavirus, Coronavirus Infections, Severe Acute Respiratory Syndrome.
- physiology : Coronavirus, Coronavirus 229E, Human, SARS Virus.
- virology : Bronchi, Coronavirus Infections, Epithelial Cells, Lung, Severe Acute Respiratory Syndrome.
- Cell Line, Humans, Immunity, Innate, Organ Culture Techniques, Viral Tropism, Virus Replication.
Abstract
Since April 2012, there have been 17 laboratory-confirmed human cases of respiratory disease associated with newly recognized human betacoronavirus lineage C virus EMC (HCoV-EMC), and 7 of them were fatal. The transmissibility and pathogenesis of HCoV-EMC remain poorly understood, and elucidating its cellular tropism in human respiratory tissues will provide mechanistic insights into the key cellular targets for virus propagation and spread. We utilized ex vivo cultures of human bronchial and lung tissue specimens to investigate the tissue tropism and virus replication kinetics following experimental infection with HCoV-EMC compared with those following infection with human coronavirus 229E (HCoV-229E) and severe acute respiratory syndrome coronavirus (SARS-CoV). The innate immune responses elicited by HCoV-EMC were also investigated. HCoV-EMC productively replicated in human bronchial and lung ex vivo organ cultures. While SARS-CoV productively replicated in lung tissue, replication in human bronchial tissue was limited. Immunohistochemistry revealed that HCoV-EMC infected nonciliated bronchial epithelium, bronchiolar epithelial cells, alveolar epithelial cells, and endothelial cells. Transmission electron microscopy showed virions within the cytoplasm of bronchial epithelial cells and budding virions from alveolar epithelial cells (type II). In contrast, there was minimal HCoV-229E infection in these tissues. HCoV-EMC failed to elicit strong type I or III interferon (IFN) or proinflammatory innate immune responses in ex vivo respiratory tissue cultures. Treatment of human lung tissue ex vivo organ cultures with type I IFNs (alpha and beta IFNs) at 1 h postinfection reduced the replication of HCoV-EMC, suggesting a potential therapeutic use of IFNs for treatment of human infection.
DOI: 10.1128/JVI.00009-13
PubMed: 23552422
Affiliations:
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Chan</name><affiliation wicri:level="1"><nlm:affiliation>Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Michael C W" sort="Chan, Michael C W" uniqKey="Chan M" first="Michael C W" last="Chan">Michael C W. Chan</name></author><author><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name></author><author><name sortKey="Chan, Louisa L Y" sort="Chan, Louisa L Y" uniqKey="Chan L" first="Louisa L Y" last="Chan">Louisa L Y. Chan</name></author><author><name sortKey="Kuok, Denise I T" sort="Kuok, Denise I T" uniqKey="Kuok D" first="Denise I T" last="Kuok">Denise I T. Kuok</name></author><author><name sortKey="Fong, Joanne H M" sort="Fong, Joanne H M" uniqKey="Fong J" first="Joanne H M" last="Fong">Joanne H M. Fong</name></author><author><name sortKey="Guan, Y" sort="Guan, Y" uniqKey="Guan Y" first="Y" last="Guan">Y. Guan</name></author><author><name sortKey="Poon, Leo L M" sort="Poon, Leo L M" uniqKey="Poon L" first="Leo L M" last="Poon">Leo L M. Poon</name></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name></author><author><name sortKey="Nicholls, John M" sort="Nicholls, John M" uniqKey="Nicholls J" first="John M" last="Nicholls">John M. 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(virology)</term><term>Organ Culture Techniques</term><term>Receptors, Virus (metabolism)</term><term>SARS Virus (physiology)</term><term>Severe Acute Respiratory Syndrome (immunology)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Viral Tropism</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Bronches (cytologie)</term><term>Bronches (virologie)</term><term>Cellules épithéliales (virologie)</term><term>Coronavirus ()</term><term>Coronavirus (génétique)</term><term>Coronavirus (immunologie)</term><term>Coronavirus (physiologie)</term><term>Coronavirus humain 229E (physiologie)</term><term>Humains</term><term>Immunité innée</term><term>Infections à coronavirus (immunologie)</term><term>Infections à coronavirus (virologie)</term><term>Interférons (pharmacologie)</term><term>Lignée cellulaire</term><term>Poumon (cytologie)</term><term>Poumon (virologie)</term><term>Récepteurs viraux (métabolisme)</term><term>Réplication virale</term><term>Syndrome respiratoire aigu sévère (immunologie)</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Techniques de culture d'organes</term><term>Tropisme viral</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Receptors, Virus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Interferons</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Bronches</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Bronchi</term><term>Lung</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Coronavirus</term><term>Infections à coronavirus</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus</term><term>Coronavirus Infections</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Récepteurs viraux</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Interférons</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus</term><term>Coronavirus humain 229E</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Coronavirus</term><term>Coronavirus 229E, Human</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Bronches</term><term>Cellules épithéliales</term><term>Infections à coronavirus</term><term>Poumon</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Bronchi</term><term>Coronavirus Infections</term><term>Epithelial Cells</term><term>Lung</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Humans</term><term>Immunity, Innate</term><term>Organ Culture Techniques</term><term>Viral Tropism</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Coronavirus</term><term>Humains</term><term>Immunité innée</term><term>Lignée cellulaire</term><term>Réplication virale</term><term>Techniques de culture d'organes</term><term>Tropisme viral</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Since April 2012, there have been 17 laboratory-confirmed human cases of respiratory disease associated with newly recognized human betacoronavirus lineage C virus EMC (HCoV-EMC), and 7 of them were fatal. The transmissibility and pathogenesis of HCoV-EMC remain poorly understood, and elucidating its cellular tropism in human respiratory tissues will provide mechanistic insights into the key cellular targets for virus propagation and spread. We utilized ex vivo cultures of human bronchial and lung tissue specimens to investigate the tissue tropism and virus replication kinetics following experimental infection with HCoV-EMC compared with those following infection with human coronavirus 229E (HCoV-229E) and severe acute respiratory syndrome coronavirus (SARS-CoV). The innate immune responses elicited by HCoV-EMC were also investigated. HCoV-EMC productively replicated in human bronchial and lung ex vivo organ cultures. While SARS-CoV productively replicated in lung tissue, replication in human bronchial tissue was limited. Immunohistochemistry revealed that HCoV-EMC infected nonciliated bronchial epithelium, bronchiolar epithelial cells, alveolar epithelial cells, and endothelial cells. Transmission electron microscopy showed virions within the cytoplasm of bronchial epithelial cells and budding virions from alveolar epithelial cells (type II). In contrast, there was minimal HCoV-229E infection in these tissues. HCoV-EMC failed to elicit strong type I or III interferon (IFN) or proinflammatory innate immune responses in ex vivo respiratory tissue cultures. Treatment of human lung tissue ex vivo organ cultures with type I IFNs (alpha and beta IFNs) at 1 h postinfection reduced the replication of HCoV-EMC, suggesting a potential therapeutic use of IFNs for treatment of human infection.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name><name sortKey="Chan, Louisa L Y" sort="Chan, Louisa L Y" uniqKey="Chan L" first="Louisa L Y" last="Chan">Louisa L Y. Chan</name><name sortKey="Chan, Michael C W" sort="Chan, Michael C W" uniqKey="Chan M" first="Michael C W" last="Chan">Michael C W. Chan</name><name sortKey="Fong, Joanne H M" sort="Fong, Joanne H M" uniqKey="Fong J" first="Joanne H M" last="Fong">Joanne H M. Fong</name><name sortKey="Guan, Y" sort="Guan, Y" uniqKey="Guan Y" first="Y" last="Guan">Y. Guan</name><name sortKey="Kuok, Denise I T" sort="Kuok, Denise I T" uniqKey="Kuok D" first="Denise I T" last="Kuok">Denise I T. Kuok</name><name sortKey="Nicholls, John M" sort="Nicholls, John M" uniqKey="Nicholls J" first="John M" last="Nicholls">John M. Nicholls</name><name sortKey="Peiris, J S Malik" sort="Peiris, J S Malik" uniqKey="Peiris J" first="J S Malik" last="Peiris">J S Malik Peiris</name><name sortKey="Poon, Leo L M" sort="Poon, Leo L M" uniqKey="Poon L" first="Leo L M" last="Poon">Leo L M. Poon</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Chan, Renee W Y" sort="Chan, Renee W Y" uniqKey="Chan R" first="Renee W Y" last="Chan">Renee W Y. Chan</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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