Importance of cholesterol-rich membrane microdomains in the interaction of the S protein of SARS-coronavirus with the cellular receptor angiotensin-converting enzyme 2.
Identifieur interne : 003092 ( Main/Exploration ); précédent : 003091; suivant : 003093Importance of cholesterol-rich membrane microdomains in the interaction of the S protein of SARS-coronavirus with the cellular receptor angiotensin-converting enzyme 2.
Auteurs : Joerg Glende [Allemagne] ; Christel Schwegmann-Wessels ; Marwan Al-Falah ; Susanne Pfefferle ; Xiuxia Qu ; Hongkui Deng ; Christian Drosten ; Hassan Y. Naim ; Georg HerrlerSource :
- Virology [ 1096-0341 ] ; 2008.
Descripteurs français
- KwdFr :
- Animaux, Cellules Caco-2, Cellules Vero, Cholestérol (métabolisme), Cyclodextrines bêta (pharmacologie), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (métabolisme), Humains, Lignée cellulaire, Microdomaines membranaires (), Microdomaines membranaires (métabolisme), Peptidyl-Dipeptidase A (métabolisme), Protéines de l'enveloppe virale (métabolisme), Pénétration virale (), Virus du SRAS (), Virus du SRAS (génétique), Virus du SRAS (métabolisme).
- MESH :
- génétique : Virus du SRAS.
- métabolisme : Cholestérol, Glycoprotéines membranaires, Microdomaines membranaires, Peptidyl-Dipeptidase A, Protéines de l'enveloppe virale, Virus du SRAS.
- pharmacologie : Cyclodextrines bêta.
- Animaux, Cellules Caco-2, Cellules Vero, Glycoprotéine de spicule des coronavirus, Humains, Lignée cellulaire, Microdomaines membranaires, Pénétration virale, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Caco-2 Cells, Cell Line, Chlorocebus aethiops, Cholesterol (metabolism), Humans, Membrane Glycoproteins (metabolism), Membrane Microdomains (chemistry), Membrane Microdomains (drug effects), Membrane Microdomains (metabolism), Peptidyl-Dipeptidase A (metabolism), SARS Virus (drug effects), SARS Virus (genetics), SARS Virus (metabolism), Spike Glycoprotein, Coronavirus, Vero Cells, Viral Envelope Proteins (metabolism), Virus Internalization (drug effects), beta-Cyclodextrins (pharmacology).
- MESH :
- chemical , metabolism : Cholesterol, Membrane Glycoproteins, Peptidyl-Dipeptidase A, Viral Envelope Proteins.
- chemistry : Membrane Microdomains.
- drug effects : Membrane Microdomains, SARS Virus, Virus Internalization.
- genetics : SARS Virus.
- metabolism : Membrane Microdomains, SARS Virus.
- chemical , pharmacology : beta-Cyclodextrins.
- Animals, Caco-2 Cells, Cell Line, Chlorocebus aethiops, Humans, Spike Glycoprotein, Coronavirus, Vero Cells.
Abstract
Cholesterol present in the plasma membrane of target cells has been shown to be important for the infection by SARS-CoV. We show that cholesterol depletion by treatment with methyl-beta-cyclodextrin (m beta CD) affects infection by SARS-CoV to the same extent as infection by vesicular stomatitis virus-based pseudotypes containing the surface glycoprotein S of SARS-CoV (VSV-Delta G-S). Therefore, the role of cholesterol for SARS-CoV infection can be assigned to the S protein and is unaffected by other coronavirus proteins. There have been contradictory reports whether or not angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV, is present in detergent-resistant membrane domains. We found that ACE2 of both Vero E6 and Caco-2 cells co-purifies with marker proteins of detergent-resistant membranes supporting the notion that cholesterol-rich microdomains provide a platform facilitating the efficient interaction of the S protein with the cellular receptor ACE2. To understand the involvement of cholesterol in the initial steps of the viral life cycle, we applied a cell-based binding assay with cells expressing the S protein and cells containing angiotensin-converting enzyme 2 (ACE2). Alternatively, we used a soluble S protein as interaction partner. Depletion of cholesterol from the ACE2-expressing cells reduced the binding of S-expressing cells by 50% whereas the binding of soluble S protein was not affected. This result suggests that optimal infection requires a multivalent interaction between viral attachment protein and cellular receptors.
DOI: 10.1016/j.virol.2008.08.026
PubMed: 18814896
Affiliations:
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Naim</name></author><author><name sortKey="Herrler, Georg" sort="Herrler, Georg" uniqKey="Herrler G" first="Georg" last="Herrler">Georg Herrler</name></author></analytic><series><title level="j">Virology</title><idno type="eISSN">1096-0341</idno><imprint><date when="2008" type="published">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Caco-2 Cells</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Cholesterol (metabolism)</term><term>Humans</term><term>Membrane Glycoproteins (metabolism)</term><term>Membrane Microdomains (chemistry)</term><term>Membrane Microdomains (drug effects)</term><term>Membrane Microdomains (metabolism)</term><term>Peptidyl-Dipeptidase A (metabolism)</term><term>SARS Virus (drug effects)</term><term>SARS Virus (genetics)</term><term>SARS Virus (metabolism)</term><term>Spike Glycoprotein, Coronavirus</term><term>Vero Cells</term><term>Viral Envelope Proteins (metabolism)</term><term>Virus Internalization (drug effects)</term><term>beta-Cyclodextrins (pharmacology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules Caco-2</term><term>Cellules Vero</term><term>Cholestérol (métabolisme)</term><term>Cyclodextrines bêta (pharmacologie)</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (métabolisme)</term><term>Humains</term><term>Lignée cellulaire</term><term>Microdomaines membranaires ()</term><term>Microdomaines membranaires (métabolisme)</term><term>Peptidyl-Dipeptidase A (métabolisme)</term><term>Protéines de l'enveloppe virale (métabolisme)</term><term>Pénétration virale ()</term><term>Virus du SRAS ()</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cholesterol</term><term>Membrane Glycoproteins</term><term>Peptidyl-Dipeptidase A</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Membrane Microdomains</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Membrane Microdomains</term><term>SARS Virus</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Membrane Microdomains</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cholestérol</term><term>Glycoprotéines membranaires</term><term>Microdomaines membranaires</term><term>Peptidyl-Dipeptidase A</term><term>Protéines de l'enveloppe virale</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Cyclodextrines bêta</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>beta-Cyclodextrins</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Caco-2 Cells</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Humans</term><term>Spike Glycoprotein, Coronavirus</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Caco-2</term><term>Cellules Vero</term><term>Glycoprotéine de spicule des coronavirus</term><term>Humains</term><term>Lignée cellulaire</term><term>Microdomaines membranaires</term><term>Pénétration virale</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cholesterol present in the plasma membrane of target cells has been shown to be important for the infection by SARS-CoV. We show that cholesterol depletion by treatment with methyl-beta-cyclodextrin (m beta CD) affects infection by SARS-CoV to the same extent as infection by vesicular stomatitis virus-based pseudotypes containing the surface glycoprotein S of SARS-CoV (VSV-Delta G-S). Therefore, the role of cholesterol for SARS-CoV infection can be assigned to the S protein and is unaffected by other coronavirus proteins. There have been contradictory reports whether or not angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV, is present in detergent-resistant membrane domains. We found that ACE2 of both Vero E6 and Caco-2 cells co-purifies with marker proteins of detergent-resistant membranes supporting the notion that cholesterol-rich microdomains provide a platform facilitating the efficient interaction of the S protein with the cellular receptor ACE2. To understand the involvement of cholesterol in the initial steps of the viral life cycle, we applied a cell-based binding assay with cells expressing the S protein and cells containing angiotensin-converting enzyme 2 (ACE2). Alternatively, we used a soluble S protein as interaction partner. Depletion of cholesterol from the ACE2-expressing cells reduced the binding of S-expressing cells by 50% whereas the binding of soluble S protein was not affected. This result suggests that optimal infection requires a multivalent interaction between viral attachment protein and cellular receptors.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>Basse-Saxe</li></region><settlement><li>Hanovre</li></settlement></list><tree><noCountry><name sortKey="Al Falah, Marwan" sort="Al Falah, Marwan" uniqKey="Al Falah M" first="Marwan" last="Al-Falah">Marwan Al-Falah</name><name sortKey="Deng, Hongkui" sort="Deng, Hongkui" uniqKey="Deng H" first="Hongkui" last="Deng">Hongkui Deng</name><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><name sortKey="Herrler, Georg" sort="Herrler, Georg" uniqKey="Herrler G" first="Georg" last="Herrler">Georg Herrler</name><name sortKey="Naim, Hassan Y" sort="Naim, Hassan Y" uniqKey="Naim H" first="Hassan Y" last="Naim">Hassan Y. Naim</name><name sortKey="Pfefferle, Susanne" sort="Pfefferle, Susanne" uniqKey="Pfefferle S" first="Susanne" last="Pfefferle">Susanne Pfefferle</name><name sortKey="Qu, Xiuxia" sort="Qu, Xiuxia" uniqKey="Qu X" first="Xiuxia" last="Qu">Xiuxia Qu</name><name sortKey="Schwegmann Wessels, Christel" sort="Schwegmann Wessels, Christel" uniqKey="Schwegmann Wessels C" first="Christel" last="Schwegmann-Wessels">Christel Schwegmann-Wessels</name></noCountry><country name="Allemagne"><region name="Basse-Saxe"><name sortKey="Glende, Joerg" sort="Glende, Joerg" uniqKey="Glende J" first="Joerg" last="Glende">Joerg Glende</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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