A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury.
Identifieur interne : 004954 ( Main/Exploration ); précédent : 004953; suivant : 004955A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury.
Auteurs : Keiji Kuba [Autriche] ; Yumiko Imai ; Shuan Rao ; Hong Gao ; Feng Guo ; Bin Guan ; Yi Huan ; Peng Yang ; Yanli Zhang ; Wei Deng ; Linlin Bao ; Binlin Zhang ; Guang Liu ; Zhong Wang ; Mark Chappell ; Yanxin Liu ; Dexian Zheng ; Andreas Leibbrandt ; Teiji Wada ; Arthur S. Slutsky ; Depei Liu ; Chuan Qin ; Chengyu Jiang ; Josef M. PenningerSource :
- Nature medicine [ 1078-8956 ] ; 2005.
Descripteurs français
- KwdFr :
- Analyse de variance, Animaux, Carboxypeptidases (métabolisme), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (métabolisme), Immunohistochimie, Maladies pulmonaires (anatomopathologie), Maladies pulmonaires (enzymologie), Maladies pulmonaires (étiologie), Peptidyl-Dipeptidase A, Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (métabolisme), Souris, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (enzymologie), Virus du SRAS (génétique), Virus du SRAS (métabolisme).
- MESH :
- anatomopathologie : Maladies pulmonaires.
- enzymologie : Maladies pulmonaires, Syndrome respiratoire aigu sévère.
- génétique : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Virus du SRAS.
- métabolisme : Carboxypeptidases, Glycoprotéines membranaires, Protéines de l'enveloppe virale, Virus du SRAS.
- étiologie : Maladies pulmonaires.
- Analyse de variance, Animaux, Glycoprotéine de spicule des coronavirus, Immunohistochimie, Peptidyl-Dipeptidase A, Souris, Syndrome respiratoire aigu sévère.
English descriptors
- KwdEn :
- Analysis of Variance, Animals, Carboxypeptidases (metabolism), Immunohistochemistry, Lung Diseases (enzymology), Lung Diseases (etiology), Lung Diseases (pathology), Membrane Glycoproteins (genetics), Membrane Glycoproteins (metabolism), Mice, Peptidyl-Dipeptidase A, SARS Virus (genetics), SARS Virus (metabolism), Severe Acute Respiratory Syndrome (complications), Severe Acute Respiratory Syndrome (enzymology), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (genetics), Viral Envelope Proteins (metabolism).
- MESH :
- chemical , genetics : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , metabolism : Carboxypeptidases, Membrane Glycoproteins, Viral Envelope Proteins.
- complications : Severe Acute Respiratory Syndrome.
- enzymology : Lung Diseases, Severe Acute Respiratory Syndrome.
- etiology : Lung Diseases.
- genetics : SARS Virus.
- metabolism : SARS Virus.
- pathology : Lung Diseases.
- Analysis of Variance, Animals, Immunohistochemistry, Mice, Peptidyl-Dipeptidase A, Spike Glycoprotein, Coronavirus.
Abstract
During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world. A new coronavirus (SARS-CoV) was identified as the SARS pathogen, which triggered severe pneumonia and acute, often lethal, lung failure. Moreover, among infected individuals influenza such as the Spanish flu and the emergence of new respiratory disease viruses have caused high lethality resulting from acute lung failure. In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor. The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses.
DOI: 10.1038/nm1267
PubMed: 16007097
Affiliations:
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Le document en format XML
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Penninger</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2005">2005</date><idno type="RBID">pubmed:16007097</idno><idno type="pmid">16007097</idno><idno type="doi">10.1038/nm1267</idno><idno type="wicri:Area/PubMed/Corpus">002651</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002651</idno><idno type="wicri:Area/PubMed/Curation">002651</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002651</idno><idno type="wicri:Area/PubMed/Checkpoint">002865</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002865</idno><idno type="wicri:Area/Ncbi/Merge">001049</idno><idno type="wicri:Area/Ncbi/Curation">001049</idno><idno type="wicri:Area/Ncbi/Checkpoint">001049</idno><idno type="wicri:doubleKey">1078-8956:2005:Kuba K:a:crucial:role</idno><idno type="wicri:Area/Main/Merge">004C81</idno><idno type="wicri:Area/Main/Curation">004954</idno><idno type="wicri:Area/Main/Exploration">004954</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury.</title><author><name sortKey="Kuba, Keiji" sort="Kuba, Keiji" uniqKey="Kuba K" first="Keiji" last="Kuba">Keiji Kuba</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-gasse 7, A-1030 Vienna, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-gasse 7, A-1030 Vienna</wicri:regionArea><wicri:noRegion>A-1030 Vienna</wicri:noRegion></affiliation></author><author><name sortKey="Imai, Yumiko" sort="Imai, Yumiko" uniqKey="Imai Y" first="Yumiko" last="Imai">Yumiko Imai</name></author><author><name sortKey="Rao, Shuan" sort="Rao, Shuan" uniqKey="Rao S" first="Shuan" last="Rao">Shuan Rao</name></author><author><name sortKey="Gao, Hong" sort="Gao, Hong" uniqKey="Gao H" first="Hong" last="Gao">Hong Gao</name></author><author><name sortKey="Guo, Feng" sort="Guo, Feng" uniqKey="Guo F" first="Feng" last="Guo">Feng Guo</name></author><author><name sortKey="Guan, Bin" sort="Guan, Bin" uniqKey="Guan B" first="Bin" last="Guan">Bin Guan</name></author><author><name sortKey="Huan, Yi" sort="Huan, Yi" uniqKey="Huan Y" first="Yi" last="Huan">Yi Huan</name></author><author><name sortKey="Yang, Peng" sort="Yang, Peng" uniqKey="Yang P" first="Peng" last="Yang">Peng Yang</name></author><author><name sortKey="Zhang, Yanli" sort="Zhang, Yanli" uniqKey="Zhang Y" first="Yanli" last="Zhang">Yanli Zhang</name></author><author><name sortKey="Deng, Wei" sort="Deng, Wei" uniqKey="Deng W" first="Wei" last="Deng">Wei Deng</name></author><author><name sortKey="Bao, Linlin" sort="Bao, Linlin" uniqKey="Bao L" first="Linlin" last="Bao">Linlin Bao</name></author><author><name sortKey="Zhang, Binlin" sort="Zhang, Binlin" uniqKey="Zhang B" first="Binlin" last="Zhang">Binlin Zhang</name></author><author><name sortKey="Liu, Guang" sort="Liu, Guang" uniqKey="Liu G" first="Guang" last="Liu">Guang Liu</name></author><author><name sortKey="Wang, Zhong" sort="Wang, Zhong" uniqKey="Wang Z" first="Zhong" last="Wang">Zhong Wang</name></author><author><name sortKey="Chappell, Mark" sort="Chappell, Mark" uniqKey="Chappell M" first="Mark" last="Chappell">Mark Chappell</name></author><author><name sortKey="Liu, Yanxin" sort="Liu, Yanxin" uniqKey="Liu Y" first="Yanxin" last="Liu">Yanxin Liu</name></author><author><name sortKey="Zheng, Dexian" sort="Zheng, Dexian" uniqKey="Zheng D" first="Dexian" last="Zheng">Dexian Zheng</name></author><author><name sortKey="Leibbrandt, Andreas" sort="Leibbrandt, Andreas" uniqKey="Leibbrandt A" first="Andreas" last="Leibbrandt">Andreas Leibbrandt</name></author><author><name sortKey="Wada, Teiji" sort="Wada, Teiji" uniqKey="Wada T" first="Teiji" last="Wada">Teiji Wada</name></author><author><name sortKey="Slutsky, Arthur S" sort="Slutsky, Arthur S" uniqKey="Slutsky A" first="Arthur S" last="Slutsky">Arthur S. Slutsky</name></author><author><name sortKey="Liu, Depei" sort="Liu, Depei" uniqKey="Liu D" first="Depei" last="Liu">Depei Liu</name></author><author><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name></author><author><name sortKey="Jiang, Chengyu" sort="Jiang, Chengyu" uniqKey="Jiang C" first="Chengyu" last="Jiang">Chengyu Jiang</name></author><author><name sortKey="Penninger, Josef M" sort="Penninger, Josef M" uniqKey="Penninger J" first="Josef M" last="Penninger">Josef M. Penninger</name></author></analytic><series><title level="j">Nature medicine</title><idno type="ISSN">1078-8956</idno><imprint><date when="2005" type="published">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Analysis of Variance</term><term>Animals</term><term>Carboxypeptidases (metabolism)</term><term>Immunohistochemistry</term><term>Lung Diseases (enzymology)</term><term>Lung Diseases (etiology)</term><term>Lung Diseases (pathology)</term><term>Membrane Glycoproteins (genetics)</term><term>Membrane Glycoproteins (metabolism)</term><term>Mice</term><term>Peptidyl-Dipeptidase A</term><term>SARS Virus (genetics)</term><term>SARS Virus (metabolism)</term><term>Severe Acute Respiratory Syndrome (complications)</term><term>Severe Acute Respiratory Syndrome (enzymology)</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (genetics)</term><term>Viral Envelope Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de variance</term><term>Animaux</term><term>Carboxypeptidases (métabolisme)</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (génétique)</term><term>Glycoprotéines membranaires (métabolisme)</term><term>Immunohistochimie</term><term>Maladies pulmonaires (anatomopathologie)</term><term>Maladies pulmonaires (enzymologie)</term><term>Maladies pulmonaires (étiologie)</term><term>Peptidyl-Dipeptidase A</term><term>Protéines de l'enveloppe virale (génétique)</term><term>Protéines de l'enveloppe virale (métabolisme)</term><term>Souris</term><term>Syndrome respiratoire aigu sévère ()</term><term>Syndrome respiratoire aigu sévère (enzymologie)</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Carboxypeptidases</term><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Maladies pulmonaires</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Maladies pulmonaires</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Lung Diseases</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Lung Diseases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Carboxypeptidases</term><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung Diseases</term></keywords><keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Maladies pulmonaires</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Analysis of Variance</term><term>Animals</term><term>Immunohistochemistry</term><term>Mice</term><term>Peptidyl-Dipeptidase A</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de variance</term><term>Animaux</term><term>Glycoprotéine de spicule des coronavirus</term><term>Immunohistochimie</term><term>Peptidyl-Dipeptidase A</term><term>Souris</term><term>Syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world. A new coronavirus (SARS-CoV) was identified as the SARS pathogen, which triggered severe pneumonia and acute, often lethal, lung failure. Moreover, among infected individuals influenza such as the Spanish flu and the emergence of new respiratory disease viruses have caused high lethality resulting from acute lung failure. In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor. The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses.</div></front></TEI><affiliations><list><country><li>Autriche</li></country></list><tree><noCountry><name sortKey="Bao, Linlin" sort="Bao, Linlin" uniqKey="Bao L" first="Linlin" last="Bao">Linlin Bao</name><name sortKey="Chappell, Mark" sort="Chappell, Mark" uniqKey="Chappell M" first="Mark" last="Chappell">Mark Chappell</name><name sortKey="Deng, Wei" sort="Deng, Wei" uniqKey="Deng W" first="Wei" last="Deng">Wei Deng</name><name sortKey="Gao, Hong" sort="Gao, Hong" uniqKey="Gao H" first="Hong" last="Gao">Hong Gao</name><name sortKey="Guan, Bin" sort="Guan, Bin" uniqKey="Guan B" first="Bin" last="Guan">Bin Guan</name><name sortKey="Guo, Feng" sort="Guo, Feng" uniqKey="Guo F" first="Feng" last="Guo">Feng Guo</name><name sortKey="Huan, Yi" sort="Huan, Yi" uniqKey="Huan Y" first="Yi" last="Huan">Yi Huan</name><name sortKey="Imai, Yumiko" sort="Imai, Yumiko" uniqKey="Imai Y" first="Yumiko" last="Imai">Yumiko Imai</name><name sortKey="Jiang, Chengyu" sort="Jiang, Chengyu" uniqKey="Jiang C" first="Chengyu" last="Jiang">Chengyu Jiang</name><name sortKey="Leibbrandt, Andreas" sort="Leibbrandt, Andreas" uniqKey="Leibbrandt A" first="Andreas" last="Leibbrandt">Andreas Leibbrandt</name><name sortKey="Liu, Depei" sort="Liu, Depei" uniqKey="Liu D" first="Depei" last="Liu">Depei Liu</name><name sortKey="Liu, Guang" sort="Liu, Guang" uniqKey="Liu G" first="Guang" last="Liu">Guang Liu</name><name sortKey="Liu, Yanxin" sort="Liu, Yanxin" uniqKey="Liu Y" first="Yanxin" last="Liu">Yanxin Liu</name><name sortKey="Penninger, Josef M" sort="Penninger, Josef M" uniqKey="Penninger J" first="Josef M" last="Penninger">Josef M. Penninger</name><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><name sortKey="Rao, Shuan" sort="Rao, Shuan" uniqKey="Rao S" first="Shuan" last="Rao">Shuan Rao</name><name sortKey="Slutsky, Arthur S" sort="Slutsky, Arthur S" uniqKey="Slutsky A" first="Arthur S" last="Slutsky">Arthur S. Slutsky</name><name sortKey="Wada, Teiji" sort="Wada, Teiji" uniqKey="Wada T" first="Teiji" last="Wada">Teiji Wada</name><name sortKey="Wang, Zhong" sort="Wang, Zhong" uniqKey="Wang Z" first="Zhong" last="Wang">Zhong Wang</name><name sortKey="Yang, Peng" sort="Yang, Peng" uniqKey="Yang P" first="Peng" last="Yang">Peng Yang</name><name sortKey="Zhang, Binlin" sort="Zhang, Binlin" uniqKey="Zhang B" first="Binlin" last="Zhang">Binlin Zhang</name><name sortKey="Zhang, Yanli" sort="Zhang, Yanli" uniqKey="Zhang Y" first="Yanli" last="Zhang">Yanli Zhang</name><name sortKey="Zheng, Dexian" sort="Zheng, Dexian" uniqKey="Zheng D" first="Dexian" last="Zheng">Dexian Zheng</name></noCountry><country name="Autriche"><noRegion><name sortKey="Kuba, Keiji" sort="Kuba, Keiji" uniqKey="Kuba K" first="Keiji" last="Kuba">Keiji Kuba</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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