Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome
Identifieur interne : 001245 ( Main/Exploration ); précédent : 001244; suivant : 001246Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome
Auteurs : Jose L. Nieto-Torres [Espagne] ; Carmina Verdiá-Báguena [Espagne] ; Jose M. Jimenez-Guarde O [Espagne] ; Jose A. Regla-Nava [Espagne] ; Carlos Casta O-Rodriguez [Espagne] ; Raul Fernandez-Delgado [Espagne] ; Jaume Torres [Singapour] ; Vicente M. Aguilella [Espagne] ; Luis Enjuanes [Espagne]Source :
- Virology [ 0042-6822 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Calcium (métabolisme), Canaux calciques (métabolisme), Cellules Vero, Inflammasomes (métabolisme), Ions (métabolisme), Mutation, Protéine-3 de la famille des NLR contenant un domaine pyrine, Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (métabolisme), Protéines de transport (métabolisme), Syndrome respiratoire aigu sévère (métabolisme), Syndrome respiratoire aigu sévère (virologie), Transport biologique, Virus du SRAS (génétique), Virus du SRAS (métabolisme).
- MESH :
- génétique : Protéines de l'enveloppe virale, Virus du SRAS.
- métabolisme : Calcium, Canaux calciques, Inflammasomes, Ions, Protéines de l'enveloppe virale, Protéines de transport, Syndrome respiratoire aigu sévère, Virus du SRAS.
- virologie : Syndrome respiratoire aigu sévère.
- Animaux, Cellules Vero, Mutation, Protéine-3 de la famille des NLR contenant un domaine pyrine, Transport biologique.
English descriptors
- KwdEn :
- Animals, Biological Transport, Calcium (metabolism), Calcium Channels (metabolism), Carrier Proteins (metabolism), Chlorocebus aethiops, Inflammasomes (metabolism), Ions (metabolism), Mutation, NLR Family, Pyrin Domain-Containing 3 Protein, SARS Virus (genetics), SARS Virus (metabolism), Severe Acute Respiratory Syndrome (metabolism), Severe Acute Respiratory Syndrome (virology), Vero Cells, Viral Envelope Proteins (genetics), Viral Envelope Proteins (metabolism).
- MESH :
- chemical , genetics : Viral Envelope Proteins.
- chemical , metabolism : Calcium, Calcium Channels, Carrier Proteins, Inflammasomes, Ions, Viral Envelope Proteins.
- genetics : SARS Virus.
- metabolism : SARS Virus, Severe Acute Respiratory Syndrome.
- virology : Severe Acute Respiratory Syndrome.
- Animals, Biological Transport, Chlorocebus aethiops, Mutation, NLR Family, Pyrin Domain-Containing 3 Protein, Vero Cells.
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a viroporin involved in virulence. E protein ion channel (IC) activity is specifically correlated with enhanced pulmonary damage, edema accumulation and death. IL-1β driven proinflammation is associated with those pathological signatures, however its link to IC activity remains unknown. In this report, we demonstrate that SARS-CoV E protein forms protein–lipid channels in ERGIC/Golgi membranes that are permeable to calcium ions, a highly relevant feature never reported before. Calcium ions together with pH modulated E protein pore charge and selectivity. Interestingly, E protein IC activity boosted the activation of the NLRP3 inflammasome, leading to IL-1β overproduction. Calcium transport through the E protein IC was the main trigger of this process. These findings strikingly link SARS-CoV E protein IC induced ionic disturbances at the cell level to immunopathological consequences and disease worsening in the infected organism.
Url:
DOI: 10.1016/j.virol.2015.08.010
PubMed: 26331680
PubMed Central: 4619128
Affiliations:
- Espagne, Singapour
- Communauté de Madrid, Communauté valencienne
- Madrid
- Université autonome de Madrid
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Le document en format XML
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Nieto-Torres</name><affiliation wicri:level="4"><nlm:aff id="aff0005">Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté de Madrid</region><settlement type="city">Madrid</settlement></placeName><orgName type="university">Université autonome de Madrid</orgName></affiliation></author><author><name sortKey="Verdia Baguena, Carmina" sort="Verdia Baguena, Carmina" uniqKey="Verdia Baguena C" first="Carmina" last="Verdiá-Báguena">Carmina Verdiá-Báguena</name><affiliation wicri:level="2"><nlm:aff id="aff0010">Department of Physics, Laboratory of Molecular Biophysics. Universitat Jaume I, 12071 Castellón, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Physics, Laboratory of Molecular Biophysics. Universitat Jaume I, 12071 Castellón</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté valencienne</region></placeName></affiliation></author><author><name sortKey="Jimenez Guarde O, Jose M" sort="Jimenez Guarde O, Jose M" uniqKey="Jimenez Guarde O J" first="Jose M." last="Jimenez-Guarde O">Jose M. Jimenez-Guarde O</name><affiliation wicri:level="4"><nlm:aff id="aff0005">Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté de Madrid</region><settlement type="city">Madrid</settlement></placeName><orgName type="university">Université autonome de Madrid</orgName></affiliation></author><author><name sortKey="Regla Nava, Jose A" sort="Regla Nava, Jose A" uniqKey="Regla Nava J" first="Jose A." last="Regla-Nava">Jose A. Regla-Nava</name><affiliation wicri:level="4"><nlm:aff id="aff0005">Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté de Madrid</region><settlement type="city">Madrid</settlement></placeName><orgName type="university">Université autonome de Madrid</orgName></affiliation></author><author><name sortKey="Casta O Rodriguez, Carlos" sort="Casta O Rodriguez, Carlos" uniqKey="Casta O Rodriguez C" first="Carlos" last="Casta O-Rodriguez">Carlos Casta O-Rodriguez</name><affiliation wicri:level="4"><nlm:aff id="aff0005">Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté de Madrid</region><settlement type="city">Madrid</settlement></placeName><orgName type="university">Université autonome de Madrid</orgName></affiliation></author><author><name sortKey="Fernandez Delgado, Raul" sort="Fernandez Delgado, Raul" uniqKey="Fernandez Delgado R" first="Raul" last="Fernandez-Delgado">Raul Fernandez-Delgado</name><affiliation wicri:level="4"><nlm:aff id="aff0005">Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté de Madrid</region><settlement type="city">Madrid</settlement></placeName><orgName type="university">Université autonome de Madrid</orgName></affiliation></author><author><name sortKey="Torres, Jaume" sort="Torres, Jaume" uniqKey="Torres J" first="Jaume" last="Torres">Jaume Torres</name><affiliation wicri:level="1"><nlm:aff id="aff0015">School of Biological Sciences, Division of Structural and Computational Biology, Nanyang Technological University, Singapore 637551, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>School of Biological Sciences, Division of Structural and Computational Biology, Nanyang Technological University, Singapore 637551</wicri:regionArea><wicri:noRegion>Singapore 637551</wicri:noRegion></affiliation></author><author><name sortKey="Aguilella, Vicente M" sort="Aguilella, Vicente M" uniqKey="Aguilella V" first="Vicente M." last="Aguilella">Vicente M. Aguilella</name><affiliation wicri:level="2"><nlm:aff id="aff0010">Department of Physics, Laboratory of Molecular Biophysics. Universitat Jaume I, 12071 Castellón, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Physics, Laboratory of Molecular Biophysics. Universitat Jaume I, 12071 Castellón</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté valencienne</region></placeName></affiliation></author><author><name sortKey="Enjuanes, Luis" sort="Enjuanes, Luis" uniqKey="Enjuanes L" first="Luis" last="Enjuanes">Luis Enjuanes</name><affiliation wicri:level="4"><nlm:aff id="aff0005">Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid</wicri:regionArea><placeName><region nuts="2" type="communauté">Communauté de Madrid</region><settlement type="city">Madrid</settlement></placeName><orgName type="university">Université autonome de Madrid</orgName></affiliation></author></analytic><series><title level="j">Virology</title><idno type="ISSN">0042-6822</idno><idno type="eISSN">1096-0341</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Biological Transport</term><term>Calcium (metabolism)</term><term>Calcium Channels (metabolism)</term><term>Carrier Proteins (metabolism)</term><term>Chlorocebus aethiops</term><term>Inflammasomes (metabolism)</term><term>Ions (metabolism)</term><term>Mutation</term><term>NLR Family, Pyrin Domain-Containing 3 Protein</term><term>SARS Virus (genetics)</term><term>SARS Virus (metabolism)</term><term>Severe Acute Respiratory Syndrome (metabolism)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Vero Cells</term><term>Viral Envelope Proteins (genetics)</term><term>Viral Envelope Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Calcium (métabolisme)</term><term>Canaux calciques (métabolisme)</term><term>Cellules Vero</term><term>Inflammasomes (métabolisme)</term><term>Ions (métabolisme)</term><term>Mutation</term><term>Protéine-3 de la famille des NLR contenant un domaine pyrine</term><term>Protéines de l'enveloppe virale (génétique)</term><term>Protéines de l'enveloppe virale (métabolisme)</term><term>Protéines de transport (métabolisme)</term><term>Syndrome respiratoire aigu sévère (métabolisme)</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Transport biologique</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>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calcium</term><term>Calcium Channels</term><term>Carrier Proteins</term><term>Inflammasomes</term><term>Ions</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><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><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Calcium</term><term>Canaux calciques</term><term>Inflammasomes</term><term>Ions</term><term>Protéines de l'enveloppe virale</term><term>Protéines de transport</term><term>Syndrome respiratoire aigu sévère</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Biological Transport</term><term>Chlorocebus aethiops</term><term>Mutation</term><term>NLR Family, Pyrin Domain-Containing 3 Protein</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Mutation</term><term>Protéine-3 de la famille des NLR contenant un domaine pyrine</term><term>Transport biologique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a viroporin involved in virulence. E protein ion channel (IC) activity is specifically correlated with enhanced pulmonary damage, edema accumulation and death. IL-1β driven proinflammation is associated with those pathological signatures, however its link to IC activity remains unknown. In this report, we demonstrate that SARS-CoV E protein forms protein–lipid channels in ERGIC/Golgi membranes that are permeable to calcium ions, a highly relevant feature never reported before. Calcium ions together with pH modulated E protein pore charge and selectivity. Interestingly, E protein IC activity boosted the activation of the NLRP3 inflammasome, leading to IL-1β overproduction. Calcium transport through the E protein IC was the main trigger of this process. These findings strikingly link SARS-CoV E protein IC induced ionic disturbances at the cell level to immunopathological consequences and disease worsening in the infected organism.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Alcaraz, A" uniqKey="Alcaraz A">A. Alcaraz</name></author><author><name sortKey="Nestorovich, E M" uniqKey="Nestorovich E">E.M. Nestorovich</name></author><author><name sortKey="Lopez, M L" uniqKey="Lopez M">M.L. Lopez</name></author><author><name sortKey="Garcia Gimenez, E" uniqKey="Garcia Gimenez E">E. Garcia-Gimenez</name></author><author><name sortKey="Bezrukov, S M" uniqKey="Bezrukov S">S.M. Bezrukov</name></author><author><name sortKey="Aguilella, V M" uniqKey="Aguilella V">V.M. Aguilella</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Almazan, F" uniqKey="Almazan F">F. Almazan</name></author><author><name sortKey="Dediego, M L" uniqKey="Dediego M">M.L. 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Aguilella</name><name sortKey="Casta O Rodriguez, Carlos" sort="Casta O Rodriguez, Carlos" uniqKey="Casta O Rodriguez C" first="Carlos" last="Casta O-Rodriguez">Carlos Casta O-Rodriguez</name><name sortKey="Enjuanes, Luis" sort="Enjuanes, Luis" uniqKey="Enjuanes L" first="Luis" last="Enjuanes">Luis Enjuanes</name><name sortKey="Fernandez Delgado, Raul" sort="Fernandez Delgado, Raul" uniqKey="Fernandez Delgado R" first="Raul" last="Fernandez-Delgado">Raul Fernandez-Delgado</name><name sortKey="Jimenez Guarde O, Jose M" sort="Jimenez Guarde O, Jose M" uniqKey="Jimenez Guarde O J" first="Jose M." last="Jimenez-Guarde O">Jose M. Jimenez-Guarde O</name><name sortKey="Regla Nava, Jose A" sort="Regla Nava, Jose A" uniqKey="Regla Nava J" first="Jose A." last="Regla-Nava">Jose A. Regla-Nava</name><name sortKey="Verdia Baguena, Carmina" sort="Verdia Baguena, Carmina" uniqKey="Verdia Baguena C" first="Carmina" last="Verdiá-Báguena">Carmina Verdiá-Báguena</name></country><country name="Singapour"><noRegion><name sortKey="Torres, Jaume" sort="Torres, Jaume" uniqKey="Torres J" first="Jaume" last="Torres">Jaume Torres</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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