Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential
Identifieur interne : 001946 ( Main/Exploration ); précédent : 001945; suivant : 001947Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential
Auteurs : Eveline Kindler ; Hulda R. J Nsd Ttir ; Doreen Muth ; Ole J. Hamming ; Rune Hartmann ; Regulo Rodriguez ; Robert Geffers ; Ron A. M. Fouchier ; Christian Drosten ; Marcel A. Müller ; Ronald Dijkman ; Volker ThielSource :
- mBio [ 2150-7511 ] ; 2013.
Descripteurs français
- KwdFr :
- ARN messager (biosynthèse), ARN messager (génétique), ARN viral (biosynthèse), ARN viral (génétique), Analyse de séquence d'ARN, Animaux, Cellules épithéliales (virologie), Coronaviridae (croissance et développement), Coronaviridae (isolement et purification), Coronaviridae (pathogénicité), Coronaviridae (physiologie), Cytokines (biosynthèse), Humains, Infections de l'appareil respiratoire (virologie), Infections à coronavirus (virologie), Moyen Orient, RT-PCR, Réplication virale, Zoonoses (virologie), Échappement immunitaire.
- MESH :
- biosynthèse : ARN messager, ARN viral, Cytokines.
- croissance et développement : Coronaviridae.
- génétique : ARN messager, ARN viral.
- isolement et purification : Coronaviridae.
- pathogénicité : Coronaviridae.
- physiologie : Coronaviridae.
- virologie : Cellules épithéliales, Infections de l'appareil respiratoire, Infections à coronavirus, Zoonoses.
- Analyse de séquence d'ARN, Animaux, Humains, Moyen Orient, RT-PCR, Réplication virale, Échappement immunitaire.
English descriptors
- KwdEn :
- Animals, Coronaviridae (growth & development), Coronaviridae (isolation & purification), Coronaviridae (pathogenicity), Coronaviridae (physiology), Coronavirus Infections (virology), Cytokines (biosynthesis), Epithelial Cells (virology), Humans, Immune Evasion, Middle East, RNA, Messenger (biosynthesis), RNA, Messenger (genetics), RNA, Viral (biosynthesis), RNA, Viral (genetics), Respiratory Tract Infections (virology), Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, RNA, Virus Replication, Zoonoses (virology).
- MESH :
- chemical , biosynthesis : Cytokines, RNA, Messenger, RNA, Viral.
- chemical , genetics : RNA, Messenger, RNA, Viral.
- geographic : Middle East.
- growth & development : Coronaviridae.
- isolation & purification : Coronaviridae.
- pathogenicity : Coronaviridae.
- physiology : Coronaviridae.
- virology : Coronavirus Infections, Epithelial Cells, Respiratory Tract Infections, Zoonoses.
- Animals, Humans, Immune Evasion, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, RNA, Virus Replication.
Abstract
The recent emergence of a novel human coronavirus (HCoV-EMC) in the Middle East raised considerable concerns, as it is associated with severe acute pneumonia, renal failure, and fatal outcome and thus resembles the clinical presentation of severe acute respiratory syndrome (SARS) observed in 2002 and 2003. Like SARS-CoV, HCoV-EMC is of zoonotic origin and closely related to bat coronaviruses. The human airway epithelium (HAE) represents the entry point and primary target tissue for respiratory viruses and is highly relevant for assessing the zoonotic potential of emerging respiratory viruses, such as HCoV-EMC. Here, we show that pseudostratified HAE cultures derived from different donors are highly permissive to HCoV-EMC infection, and by using reverse transcription (RT)-PCR and RNAseq data, we experimentally determined the identity of seven HCoV-EMC subgenomic mRNAs. Although the HAE cells were readily responsive to type I and type III interferon (IFN), we observed neither a pronounced inflammatory cytokine nor any detectable IFN responses following HCoV-EMC, SARS-CoV, or HCoV-229E infection, suggesting that innate immune evasion mechanisms and putative IFN antagonists of HCoV-EMC are operational in the new host. Importantly, however, we demonstrate that both type I and type III IFN can efficiently reduce HCoV-EMC replication in HAE cultures, providing a possible treatment option in cases of suspected HCoV-EMC infection.
Url:
DOI: 10.1128/mBio.00611-12
PubMed: 23422412
PubMed Central: 3573664
Affiliations:
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Le document en format XML
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failure, and fatal outcome and thus resembles the clinical presentation of severe acute respiratory syndrome (SARS) observed in 2002 and 2003. Like SARS-CoV, HCoV-EMC is of zoonotic origin and closely related to bat coronaviruses. The human airway epithelium (HAE) represents the entry point and primary target tissue for respiratory viruses and is highly relevant for assessing the zoonotic potential of emerging respiratory viruses, such as HCoV-EMC. Here, we show that pseudostratified HAE cultures derived from different donors are highly permissive to HCoV-EMC infection, and by using reverse transcription (RT)-PCR and RNAseq data, we experimentally determined the identity of seven HCoV-EMC subgenomic mRNAs. Although the HAE cells were readily responsive to type I and type III interferon (IFN), we observed neither a pronounced inflammatory cytokine nor any detectable IFN responses following HCoV-EMC, SARS-CoV, or HCoV-229E infection, suggesting that innate immune evasion mechanisms and putative IFN antagonists of HCoV-EMC are operational in the new host. Importantly, however, we demonstrate that both type I and type III IFN can efficiently reduce HCoV-EMC replication in HAE cultures, providing a possible treatment option in cases of suspected HCoV-EMC infection.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Perlman, S" uniqKey="Perlman S">S Perlman</name></author><author><name sortKey="Netland, J" uniqKey="Netland J">J Netland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weiss, Sr" uniqKey="Weiss S">SR Weiss</name></author><author><name sortKey="Navas Martin, S" uniqKey="Navas Martin S">S Navas-Martin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="De Graaf, M" uniqKey="De Graaf M">M de Graaf</name></author><author><name sortKey="Lauber, C" uniqKey="Lauber C">C Lauber</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author><author><name sortKey="Gorbalenya, Ae" uniqKey="Gorbalenya A">AE Gorbalenya</name></author><author><name sortKey="Snijder, Ej" uniqKey="Snijder E">EJ Snijder</name></author><author><name sortKey="Fouchier, Ram" uniqKey="Fouchier R">RAM Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bermingham, A" uniqKey="Bermingham A">A Bermingham</name></author><author><name sortKey="Chand, Ma" uniqKey="Chand M">MA Chand</name></author><author><name sortKey="Brown, Cs" uniqKey="Brown C">CS Brown</name></author><author><name sortKey="Aarons, E" uniqKey="Aarons E">E 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sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A. M." last="Fouchier">Ron A. M. Fouchier</name><name sortKey="Geffers, Robert" sort="Geffers, Robert" uniqKey="Geffers R" first="Robert" last="Geffers">Robert Geffers</name><name sortKey="Hamming, Ole J" sort="Hamming, Ole J" uniqKey="Hamming O" first="Ole J." last="Hamming">Ole J. Hamming</name><name sortKey="Hartmann, Rune" sort="Hartmann, Rune" uniqKey="Hartmann R" first="Rune" last="Hartmann">Rune Hartmann</name><name sortKey="J Nsd Ttir, Hulda R" sort="J Nsd Ttir, Hulda R" uniqKey="J Nsd Ttir H" first="Hulda R." last="J Nsd Ttir">Hulda R. J Nsd Ttir</name><name sortKey="Kindler, Eveline" sort="Kindler, Eveline" uniqKey="Kindler E" first="Eveline" last="Kindler">Eveline Kindler</name><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A." last="Müller">Marcel A. Müller</name><name sortKey="Muth, Doreen" sort="Muth, Doreen" uniqKey="Muth D" first="Doreen" last="Muth">Doreen Muth</name><name sortKey="Rodriguez, Regulo" sort="Rodriguez, Regulo" uniqKey="Rodriguez R" first="Regulo" last="Rodriguez">Regulo Rodriguez</name><name sortKey="Thiel, Volker" sort="Thiel, Volker" uniqKey="Thiel V" first="Volker" last="Thiel">Volker Thiel</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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