SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death.
Identifieur interne : 000C43 ( Main/Exploration ); précédent : 000C42; suivant : 000C44SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death.
Auteurs : Yuan Yue [République populaire de Chine] ; Neel R. Nabar [États-Unis] ; Chong-Shan Shi [États-Unis] ; Olena Kamenyeva [États-Unis] ; Xun Xiao [République populaire de Chine] ; Il-Young Hwang [États-Unis] ; Min Wang [République populaire de Chine] ; John H. Kehrl [États-Unis]Source :
- Cell death & disease [ 2041-4889 ] ; 2018.
Descripteurs français
- KwdFr :
- Apoptose (physiologie), Autophagie (physiologie), Cadres ouverts de lecture (génétique), Cellules A549, Cellules HEK293, Cellules HeLa, Humains, Inflammasomes (métabolisme), Lignée cellulaire, Lignée cellulaire tumorale, Lysosomes (anatomopathologie), Lysosomes (métabolisme), Lysosomes (virologie), Membranes intracellulaires (anatomopathologie), Membranes intracellulaires (virologie), Nécrose (anatomopathologie), Nécrose (métabolisme), Nécrose (virologie), Receptor-Interacting Protein Serine-Threonine Kinases (métabolisme), Syndrome respiratoire aigu sévère (anatomopathologie), Syndrome respiratoire aigu sévère (virologie), Virus du SRAS (génétique), Virus du SRAS (pathogénicité).
- MESH :
- anatomopathologie : Lysosomes, Membranes intracellulaires, Nécrose, Syndrome respiratoire aigu sévère.
- génétique : Cadres ouverts de lecture, Virus du SRAS.
- métabolisme : Inflammasomes, Lysosomes, Nécrose, Receptor-Interacting Protein Serine-Threonine Kinases.
- pathogénicité : Virus du SRAS.
- physiologie : Apoptose, Autophagie.
- virologie : Lysosomes, Membranes intracellulaires, Nécrose, Syndrome respiratoire aigu sévère.
- Cellules A549, Cellules HEK293, Cellules HeLa, Humains, Lignée cellulaire, Lignée cellulaire tumorale.
English descriptors
- KwdEn :
- A549 Cells, Apoptosis (physiology), Autophagy (physiology), Cell Line, Cell Line, Tumor, HEK293 Cells, HeLa Cells, Humans, Inflammasomes (metabolism), Intracellular Membranes (pathology), Intracellular Membranes (virology), Lysosomes (metabolism), Lysosomes (pathology), Lysosomes (virology), Necrosis (metabolism), Necrosis (pathology), Necrosis (virology), Open Reading Frames (genetics), Receptor-Interacting Protein Serine-Threonine Kinases (metabolism), SARS Virus (genetics), SARS Virus (pathogenicity), Severe Acute Respiratory Syndrome (pathology), Severe Acute Respiratory Syndrome (virology).
- MESH :
- chemical , metabolism : Inflammasomes, Receptor-Interacting Protein Serine-Threonine Kinases.
- genetics : Open Reading Frames, SARS Virus.
- metabolism : Lysosomes, Necrosis.
- pathogenicity : SARS Virus.
- pathology : Intracellular Membranes, Lysosomes, Necrosis, Severe Acute Respiratory Syndrome.
- physiology : Apoptosis, Autophagy.
- virology : Intracellular Membranes, Lysosomes, Necrosis, Severe Acute Respiratory Syndrome.
- A549 Cells, Cell Line, Cell Line, Tumor, HEK293 Cells, HeLa Cells, Humans.
Abstract
The molecular mechanisms underlying the severe lung pathology that occurs during SARS-CoV infections remain incompletely understood. The largest of the SARS-CoV accessory protein open reading frames (SARS 3a) oligomerizes, dynamically inserting into late endosomal, lysosomal, and trans-Golgi-network membranes. While previously implicated in a non-inflammatory apoptotic cell death pathway, here we extend the range of SARS 3a pathophysiologic targets by examining its effects on necrotic cell death pathways. We show that SARS 3a interacts with Receptor Interacting Protein 3 (Rip3), which augments the oligomerization of SARS 3a helping drive necrotic cell death. In addition, by inserting into lysosomal membranes SARS 3a triggers lysosomal damage and dysfunction. Consequently, Transcription Factor EB (TFEB) translocates to the nucleus increasing the transcription of autophagy- and lysosome-related genes. Finally, SARS 3a activates caspase-1 either directly or via an enhanced potassium efflux, which triggers NLRP3 inflammasome assembly. In summary, Rip3-mediated oligomerization of SARS 3a causes necrotic cell death, lysosomal damage, and caspase-1 activation-all likely contributing to the clinical manifestations of SARS-CoV infection.
DOI: 10.1038/s41419-018-0917-y
PubMed: 30185776
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000981
- to stream PubMed, to step Curation: 000981
- to stream PubMed, to step Checkpoint: 000970
- to stream Ncbi, to step Merge: 002F60
- to stream Ncbi, to step Curation: 002F60
- to stream Ncbi, to step Checkpoint: 002F60
- to stream Main, to step Merge: 000C45
- to stream Main, to step Curation: 000C43
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death.</title>
<author><name sortKey="Yue, Yuan" sort="Yue, Yuan" uniqKey="Yue Y" first="Yuan" last="Yue">Yuan Yue</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041</wicri:regionArea>
<wicri:noRegion>610041</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nabar, Neel R" sort="Nabar, Neel R" uniqKey="Nabar N" first="Neel R" last="Nabar">Neel R. Nabar</name>
<affiliation wicri:level="1"><nlm:affiliation>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. neel.nabar@nih.gov.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892</wicri:regionArea>
<wicri:noRegion>20892</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Shi, Chong Shan" sort="Shi, Chong Shan" uniqKey="Shi C" first="Chong-Shan" last="Shi">Chong-Shan Shi</name>
<affiliation wicri:level="1"><nlm:affiliation>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892</wicri:regionArea>
<wicri:noRegion>20892</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kamenyeva, Olena" sort="Kamenyeva, Olena" uniqKey="Kamenyeva O" first="Olena" last="Kamenyeva">Olena Kamenyeva</name>
<affiliation wicri:level="1"><nlm:affiliation>Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892</wicri:regionArea>
<wicri:noRegion>20892</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Xiao, Xun" sort="Xiao, Xun" uniqKey="Xiao X" first="Xun" last="Xiao">Xun Xiao</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041</wicri:regionArea>
<wicri:noRegion>610041</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hwang, Il Young" sort="Hwang, Il Young" uniqKey="Hwang I" first="Il-Young" last="Hwang">Il-Young Hwang</name>
<affiliation wicri:level="1"><nlm:affiliation>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892</wicri:regionArea>
<wicri:noRegion>20892</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wang, Min" sort="Wang, Min" uniqKey="Wang M" first="Min" last="Wang">Min Wang</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041</wicri:regionArea>
<wicri:noRegion>610041</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kehrl, John H" sort="Kehrl, John H" uniqKey="Kehrl J" first="John H" last="Kehrl">John H. Kehrl</name>
<affiliation wicri:level="1"><nlm:affiliation>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. jkehrl@niaid.nih.gov.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892</wicri:regionArea>
<wicri:noRegion>20892</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2018">2018</date>
<idno type="RBID">pubmed:30185776</idno>
<idno type="pmid">30185776</idno>
<idno type="doi">10.1038/s41419-018-0917-y</idno>
<idno type="wicri:Area/PubMed/Corpus">000981</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000981</idno>
<idno type="wicri:Area/PubMed/Curation">000981</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000981</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000970</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000970</idno>
<idno type="wicri:Area/Ncbi/Merge">002F60</idno>
<idno type="wicri:Area/Ncbi/Curation">002F60</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">002F60</idno>
<idno type="wicri:Area/Main/Merge">000C45</idno>
<idno type="wicri:Area/Main/Curation">000C43</idno>
<idno type="wicri:Area/Main/Exploration">000C43</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death.</title>
<author><name sortKey="Yue, Yuan" sort="Yue, Yuan" uniqKey="Yue Y" first="Yuan" last="Yue">Yuan Yue</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041</wicri:regionArea>
<wicri:noRegion>610041</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nabar, Neel R" sort="Nabar, Neel R" uniqKey="Nabar N" first="Neel R" last="Nabar">Neel R. Nabar</name>
<affiliation wicri:level="1"><nlm:affiliation>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. neel.nabar@nih.gov.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892</wicri:regionArea>
<wicri:noRegion>20892</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Shi, Chong Shan" sort="Shi, Chong Shan" uniqKey="Shi C" first="Chong-Shan" last="Shi">Chong-Shan Shi</name>
<affiliation wicri:level="1"><nlm:affiliation>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892</wicri:regionArea>
<wicri:noRegion>20892</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kamenyeva, Olena" sort="Kamenyeva, Olena" uniqKey="Kamenyeva O" first="Olena" last="Kamenyeva">Olena Kamenyeva</name>
<affiliation wicri:level="1"><nlm:affiliation>Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892</wicri:regionArea>
<wicri:noRegion>20892</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Xiao, Xun" sort="Xiao, Xun" uniqKey="Xiao X" first="Xun" last="Xiao">Xun Xiao</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041</wicri:regionArea>
<wicri:noRegion>610041</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hwang, Il Young" sort="Hwang, Il Young" uniqKey="Hwang I" first="Il-Young" last="Hwang">Il-Young Hwang</name>
<affiliation wicri:level="1"><nlm:affiliation>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892</wicri:regionArea>
<wicri:noRegion>20892</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wang, Min" sort="Wang, Min" uniqKey="Wang M" first="Min" last="Wang">Min Wang</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041</wicri:regionArea>
<wicri:noRegion>610041</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kehrl, John H" sort="Kehrl, John H" uniqKey="Kehrl J" first="John H" last="Kehrl">John H. Kehrl</name>
<affiliation wicri:level="1"><nlm:affiliation>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. jkehrl@niaid.nih.gov.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892</wicri:regionArea>
<wicri:noRegion>20892</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Cell death & disease</title>
<idno type="eISSN">2041-4889</idno>
<imprint><date when="2018" type="published">2018</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>A549 Cells</term>
<term>Apoptosis (physiology)</term>
<term>Autophagy (physiology)</term>
<term>Cell Line</term>
<term>Cell Line, Tumor</term>
<term>HEK293 Cells</term>
<term>HeLa Cells</term>
<term>Humans</term>
<term>Inflammasomes (metabolism)</term>
<term>Intracellular Membranes (pathology)</term>
<term>Intracellular Membranes (virology)</term>
<term>Lysosomes (metabolism)</term>
<term>Lysosomes (pathology)</term>
<term>Lysosomes (virology)</term>
<term>Necrosis (metabolism)</term>
<term>Necrosis (pathology)</term>
<term>Necrosis (virology)</term>
<term>Open Reading Frames (genetics)</term>
<term>Receptor-Interacting Protein Serine-Threonine Kinases (metabolism)</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (pathogenicity)</term>
<term>Severe Acute Respiratory Syndrome (pathology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Apoptose (physiologie)</term>
<term>Autophagie (physiologie)</term>
<term>Cadres ouverts de lecture (génétique)</term>
<term>Cellules A549</term>
<term>Cellules HEK293</term>
<term>Cellules HeLa</term>
<term>Humains</term>
<term>Inflammasomes (métabolisme)</term>
<term>Lignée cellulaire</term>
<term>Lignée cellulaire tumorale</term>
<term>Lysosomes (anatomopathologie)</term>
<term>Lysosomes (métabolisme)</term>
<term>Lysosomes (virologie)</term>
<term>Membranes intracellulaires (anatomopathologie)</term>
<term>Membranes intracellulaires (virologie)</term>
<term>Nécrose (anatomopathologie)</term>
<term>Nécrose (métabolisme)</term>
<term>Nécrose (virologie)</term>
<term>Receptor-Interacting Protein Serine-Threonine Kinases (métabolisme)</term>
<term>Syndrome respiratoire aigu sévère (anatomopathologie)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Virus du SRAS (génétique)</term>
<term>Virus du SRAS (pathogénicité)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Inflammasomes</term>
<term>Receptor-Interacting Protein Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Lysosomes</term>
<term>Membranes intracellulaires</term>
<term>Nécrose</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Open Reading Frames</term>
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cadres ouverts de lecture</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lysosomes</term>
<term>Necrosis</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Inflammasomes</term>
<term>Lysosomes</term>
<term>Nécrose</term>
<term>Receptor-Interacting Protein Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Intracellular Membranes</term>
<term>Lysosomes</term>
<term>Necrosis</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Apoptose</term>
<term>Autophagie</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Apoptosis</term>
<term>Autophagy</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Lysosomes</term>
<term>Membranes intracellulaires</term>
<term>Nécrose</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Intracellular Membranes</term>
<term>Lysosomes</term>
<term>Necrosis</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>A549 Cells</term>
<term>Cell Line</term>
<term>Cell Line, Tumor</term>
<term>HEK293 Cells</term>
<term>HeLa Cells</term>
<term>Humans</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Cellules A549</term>
<term>Cellules HEK293</term>
<term>Cellules HeLa</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Lignée cellulaire tumorale</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The molecular mechanisms underlying the severe lung pathology that occurs during SARS-CoV infections remain incompletely understood. The largest of the SARS-CoV accessory protein open reading frames (SARS 3a) oligomerizes, dynamically inserting into late endosomal, lysosomal, and trans-Golgi-network membranes. While previously implicated in a non-inflammatory apoptotic cell death pathway, here we extend the range of SARS 3a pathophysiologic targets by examining its effects on necrotic cell death pathways. We show that SARS 3a interacts with Receptor Interacting Protein 3 (Rip3), which augments the oligomerization of SARS 3a helping drive necrotic cell death. In addition, by inserting into lysosomal membranes SARS 3a triggers lysosomal damage and dysfunction. Consequently, Transcription Factor EB (TFEB) translocates to the nucleus increasing the transcription of autophagy- and lysosome-related genes. Finally, SARS 3a activates caspase-1 either directly or via an enhanced potassium efflux, which triggers NLRP3 inflammasome assembly. In summary, Rip3-mediated oligomerization of SARS 3a causes necrotic cell death, lysosomal damage, and caspase-1 activation-all likely contributing to the clinical manifestations of SARS-CoV infection.</div>
</front>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Yue, Yuan" sort="Yue, Yuan" uniqKey="Yue Y" first="Yuan" last="Yue">Yuan Yue</name>
</noRegion>
<name sortKey="Wang, Min" sort="Wang, Min" uniqKey="Wang M" first="Min" last="Wang">Min Wang</name>
<name sortKey="Xiao, Xun" sort="Xiao, Xun" uniqKey="Xiao X" first="Xun" last="Xiao">Xun Xiao</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Nabar, Neel R" sort="Nabar, Neel R" uniqKey="Nabar N" first="Neel R" last="Nabar">Neel R. Nabar</name>
</noRegion>
<name sortKey="Hwang, Il Young" sort="Hwang, Il Young" uniqKey="Hwang I" first="Il-Young" last="Hwang">Il-Young Hwang</name>
<name sortKey="Kamenyeva, Olena" sort="Kamenyeva, Olena" uniqKey="Kamenyeva O" first="Olena" last="Kamenyeva">Olena Kamenyeva</name>
<name sortKey="Kehrl, John H" sort="Kehrl, John H" uniqKey="Kehrl J" first="John H" last="Kehrl">John H. Kehrl</name>
<name sortKey="Shi, Chong Shan" sort="Shi, Chong Shan" uniqKey="Shi C" first="Chong-Shan" last="Shi">Chong-Shan Shi</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000C43 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000C43 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= Main |étape= Exploration |type= RBID |clé= pubmed:30185776 |texte= SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:30185776" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \ | NlmPubMed2Wicri -a SrasV1
This area was generated with Dilib version V0.6.33. |