The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis.
Identifieur interne : 000F05 ( PubMed/Checkpoint ); précédent : 000F04; suivant : 000F06The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis.
Auteurs : Jose M. Jimenez-Guarde O [Espagne] ; Jose L. Nieto-Torres [Espagne] ; Marta L. Dediego [Espagne] ; Jose A. Regla-Nava [Espagne] ; Raul Fernandez-Delgado [Espagne] ; Carlos Casta O-Rodriguez [Espagne] ; Luis Enjuanes [Espagne]Source :
- PLoS pathogens [ 1553-7374 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Cellules Vero, Domaines PDZ (physiologie), Femelle, Immunoprécipitation, Interactions hôte-parasite (physiologie), Microscopie confocale, Modèles animaux de maladie humaine, Protéines de l'enveloppe virale (métabolisme), Réaction de polymérisation en chaîne, Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère (métabolisme), Syndrome respiratoire aigu sévère (virologie), Synténines (métabolisme), Séquençage par oligonucléotides en batterie, Technique de Western, Techniques de double hybride, Transduction du signal (physiologie), Virulence, Virus du SRAS (pathogénicité), p38 Mitogen-Activated Protein Kinases (métabolisme).
- MESH :
- métabolisme : Protéines de l'enveloppe virale, Syndrome respiratoire aigu sévère, Synténines, p38 Mitogen-Activated Protein Kinases.
- pathogénicité : Virus du SRAS.
- physiologie : Domaines PDZ, Interactions hôte-parasite, Transduction du signal.
- virologie : Syndrome respiratoire aigu sévère.
- Animaux, Cellules Vero, Femelle, Immunoprécipitation, Microscopie confocale, Modèles animaux de maladie humaine, Réaction de polymérisation en chaîne, Souris, Souris de lignée BALB C, Séquençage par oligonucléotides en batterie, Technique de Western, Techniques de double hybride, Virulence.
English descriptors
- KwdEn :
- Animals, Blotting, Western, Chlorocebus aethiops, Disease Models, Animal, Female, Host-Parasite Interactions (physiology), Immunoprecipitation, Mice, Mice, Inbred BALB C, Microscopy, Confocal, Oligonucleotide Array Sequence Analysis, PDZ Domains (physiology), Polymerase Chain Reaction, SARS Virus (pathogenicity), Severe Acute Respiratory Syndrome (metabolism), Severe Acute Respiratory Syndrome (virology), Signal Transduction (physiology), Syntenins (metabolism), Two-Hybrid System Techniques, Vero Cells, Viral Envelope Proteins (metabolism), Virulence, p38 Mitogen-Activated Protein Kinases (metabolism).
- MESH :
- chemical , metabolism : Syntenins, Viral Envelope Proteins, p38 Mitogen-Activated Protein Kinases.
- metabolism : Severe Acute Respiratory Syndrome.
- pathogenicity : SARS Virus.
- physiology : Host-Parasite Interactions, PDZ Domains, Signal Transduction.
- virology : Severe Acute Respiratory Syndrome.
- Animals, Blotting, Western, Chlorocebus aethiops, Disease Models, Animal, Female, Immunoprecipitation, Mice, Mice, Inbred BALB C, Microscopy, Confocal, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Two-Hybrid System Techniques, Vero Cells, Virulence.
Abstract
A recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major determinant of virulence. Elimination of SARS-CoV E protein PBM by using reverse genetics caused a reduction in the deleterious exacerbation of the immune response triggered during infection with the parental virus and virus attenuation. Cellular protein syntenin was identified to bind the E protein PBM during SARS-CoV infection by using three complementary strategies, yeast two-hybrid, reciprocal coimmunoprecipitation and confocal microscopy assays. Syntenin redistributed from the nucleus to the cell cytoplasm during infection with viruses containing the E protein PBM, activating p38 MAPK and leading to the overexpression of inflammatory cytokines. Silencing of syntenin using siRNAs led to a decrease in p38 MAPK activation in SARS-CoV infected cells, further reinforcing their functional relationship. Active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM as compared with the parental virus, leading to a decreased expression of inflammatory cytokines and to virus attenuation. Interestingly, administration of a p38 MAPK inhibitor led to an increase in mice survival after infection with SARS-CoV, confirming the relevance of this pathway in SARS-CoV virulence. Therefore, the E protein PBM is a virulence domain that activates immunopathology most likely by using syntenin as a mediator of p38 MAPK induced inflammation.
DOI: 10.1371/journal.ppat.1004320
PubMed: 25122212
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:25122212Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis.</title>
<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:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
<orgName type="university">Université autonome de Madrid</orgName>
</affiliation>
</author>
<author><name sortKey="Nieto Torres, Jose L" sort="Nieto Torres, Jose L" uniqKey="Nieto Torres J" first="Jose L" last="Nieto-Torres">Jose L. Nieto-Torres</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
<orgName type="university">Université autonome de Madrid</orgName>
</affiliation>
</author>
<author><name sortKey="Dediego, Marta L" sort="Dediego, Marta L" uniqKey="Dediego M" first="Marta L" last="Dediego">Marta L. Dediego</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</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:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</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:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</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:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
<orgName type="university">Université autonome de Madrid</orgName>
</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:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
<orgName type="university">Université autonome de Madrid</orgName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2014">2014</date>
<idno type="RBID">pubmed:25122212</idno>
<idno type="pmid">25122212</idno>
<idno type="doi">10.1371/journal.ppat.1004320</idno>
<idno type="wicri:Area/PubMed/Corpus">000F46</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000F46</idno>
<idno type="wicri:Area/PubMed/Curation">000F46</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000F46</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000F05</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000F05</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis.</title>
<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:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
<orgName type="university">Université autonome de Madrid</orgName>
</affiliation>
</author>
<author><name sortKey="Nieto Torres, Jose L" sort="Nieto Torres, Jose L" uniqKey="Nieto Torres J" first="Jose L" last="Nieto-Torres">Jose L. Nieto-Torres</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
<orgName type="university">Université autonome de Madrid</orgName>
</affiliation>
</author>
<author><name sortKey="Dediego, Marta L" sort="Dediego, Marta L" uniqKey="Dediego M" first="Marta L" last="Dediego">Marta L. Dediego</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</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:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</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:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</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:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
<orgName type="university">Université autonome de Madrid</orgName>
</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:affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
<orgName type="university">Université autonome de Madrid</orgName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS pathogens</title>
<idno type="eISSN">1553-7374</idno>
<imprint><date when="2014" type="published">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Blotting, Western</term>
<term>Chlorocebus aethiops</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Host-Parasite Interactions (physiology)</term>
<term>Immunoprecipitation</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Microscopy, Confocal</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>PDZ Domains (physiology)</term>
<term>Polymerase Chain Reaction</term>
<term>SARS Virus (pathogenicity)</term>
<term>Severe Acute Respiratory Syndrome (metabolism)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Signal Transduction (physiology)</term>
<term>Syntenins (metabolism)</term>
<term>Two-Hybrid System Techniques</term>
<term>Vero Cells</term>
<term>Viral Envelope Proteins (metabolism)</term>
<term>Virulence</term>
<term>p38 Mitogen-Activated Protein Kinases (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Cellules Vero</term>
<term>Domaines PDZ (physiologie)</term>
<term>Femelle</term>
<term>Immunoprécipitation</term>
<term>Interactions hôte-parasite (physiologie)</term>
<term>Microscopie confocale</term>
<term>Modèles animaux de maladie humaine</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>Réaction de polymérisation en chaîne</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Syndrome respiratoire aigu sévère (métabolisme)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Synténines (métabolisme)</term>
<term>Séquençage par oligonucléotides en batterie</term>
<term>Technique de Western</term>
<term>Techniques de double hybride</term>
<term>Transduction du signal (physiologie)</term>
<term>Virulence</term>
<term>Virus du SRAS (pathogénicité)</term>
<term>p38 Mitogen-Activated Protein Kinases (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Syntenins</term>
<term>Viral Envelope Proteins</term>
<term>p38 Mitogen-Activated Protein Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines de l'enveloppe virale</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Synténines</term>
<term>p38 Mitogen-Activated Protein 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="physiologie" xml:lang="fr"><term>Domaines PDZ</term>
<term>Interactions hôte-parasite</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Host-Parasite Interactions</term>
<term>PDZ Domains</term>
<term>Signal Transduction</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>Blotting, Western</term>
<term>Chlorocebus aethiops</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Immunoprecipitation</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Microscopy, Confocal</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Polymerase Chain Reaction</term>
<term>Two-Hybrid System Techniques</term>
<term>Vero Cells</term>
<term>Virulence</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules Vero</term>
<term>Femelle</term>
<term>Immunoprécipitation</term>
<term>Microscopie confocale</term>
<term>Modèles animaux de maladie humaine</term>
<term>Réaction de polymérisation en chaîne</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Séquençage par oligonucléotides en batterie</term>
<term>Technique de Western</term>
<term>Techniques de double hybride</term>
<term>Virulence</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">A recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major determinant of virulence. Elimination of SARS-CoV E protein PBM by using reverse genetics caused a reduction in the deleterious exacerbation of the immune response triggered during infection with the parental virus and virus attenuation. Cellular protein syntenin was identified to bind the E protein PBM during SARS-CoV infection by using three complementary strategies, yeast two-hybrid, reciprocal coimmunoprecipitation and confocal microscopy assays. Syntenin redistributed from the nucleus to the cell cytoplasm during infection with viruses containing the E protein PBM, activating p38 MAPK and leading to the overexpression of inflammatory cytokines. Silencing of syntenin using siRNAs led to a decrease in p38 MAPK activation in SARS-CoV infected cells, further reinforcing their functional relationship. Active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM as compared with the parental virus, leading to a decreased expression of inflammatory cytokines and to virus attenuation. Interestingly, administration of a p38 MAPK inhibitor led to an increase in mice survival after infection with SARS-CoV, confirming the relevance of this pathway in SARS-CoV virulence. Therefore, the E protein PBM is a virulence domain that activates immunopathology most likely by using syntenin as a mediator of p38 MAPK induced inflammation. </div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25122212</PMID>
<DateCompleted><Year>2015</Year>
<Month>12</Month>
<Day>21</Day>
</DateCompleted>
<DateRevised><Year>2019</Year>
<Month>12</Month>
<Day>10</Day>
</DateRevised>
<Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1553-7374</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>10</Volume>
<Issue>8</Issue>
<PubDate><Year>2014</Year>
<Month>Aug</Month>
</PubDate>
</JournalIssue>
<Title>PLoS pathogens</Title>
<ISOAbbreviation>PLoS Pathog.</ISOAbbreviation>
</Journal>
<ArticleTitle>The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis.</ArticleTitle>
<Pagination><MedlinePgn>e1004320</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.ppat.1004320</ELocationID>
<Abstract><AbstractText>A recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major determinant of virulence. Elimination of SARS-CoV E protein PBM by using reverse genetics caused a reduction in the deleterious exacerbation of the immune response triggered during infection with the parental virus and virus attenuation. Cellular protein syntenin was identified to bind the E protein PBM during SARS-CoV infection by using three complementary strategies, yeast two-hybrid, reciprocal coimmunoprecipitation and confocal microscopy assays. Syntenin redistributed from the nucleus to the cell cytoplasm during infection with viruses containing the E protein PBM, activating p38 MAPK and leading to the overexpression of inflammatory cytokines. Silencing of syntenin using siRNAs led to a decrease in p38 MAPK activation in SARS-CoV infected cells, further reinforcing their functional relationship. Active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM as compared with the parental virus, leading to a decreased expression of inflammatory cytokines and to virus attenuation. Interestingly, administration of a p38 MAPK inhibitor led to an increase in mice survival after infection with SARS-CoV, confirming the relevance of this pathway in SARS-CoV virulence. Therefore, the E protein PBM is a virulence domain that activates immunopathology most likely by using syntenin as a mediator of p38 MAPK induced inflammation. </AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Jimenez-Guardeño</LastName>
<ForeName>Jose M</ForeName>
<Initials>JM</Initials>
<AffiliationInfo><Affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nieto-Torres</LastName>
<ForeName>Jose L</ForeName>
<Initials>JL</Initials>
<AffiliationInfo><Affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>DeDiego</LastName>
<ForeName>Marta L</ForeName>
<Initials>ML</Initials>
<AffiliationInfo><Affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Regla-Nava</LastName>
<ForeName>Jose A</ForeName>
<Initials>JA</Initials>
<AffiliationInfo><Affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fernandez-Delgado</LastName>
<ForeName>Raul</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Castaño-Rodriguez</LastName>
<ForeName>Carlos</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Enjuanes</LastName>
<ForeName>Luis</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Universidad Autónoma de Madrid, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>P01 AI060699</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 AI091322</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2014</Year>
<Month>08</Month>
<Day>14</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>PLoS Pathog</MedlineTA>
<NlmUniqueID>101238921</NlmUniqueID>
<ISSNLinking>1553-7366</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C501689">E protein, SARS coronavirus</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C484513">Sdcbp protein, mouse</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D053676">Syntenins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014759">Viral Envelope Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.11.24</RegistryNumber>
<NameOfSubstance UI="D048051">p38 Mitogen-Activated Protein Kinases</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015153" MajorTopicYN="N">Blotting, Western</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006790" MajorTopicYN="N">Host-Parasite Interactions</DescriptorName>
<QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D047468" MajorTopicYN="N">Immunoprecipitation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018613" MajorTopicYN="N">Microscopy, Confocal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020411" MajorTopicYN="N">Oligonucleotide Array Sequence Analysis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054731" MajorTopicYN="N">PDZ Domains</DescriptorName>
<QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016133" MajorTopicYN="N">Polymerase Chain Reaction</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045473" MajorTopicYN="N">SARS Virus</DescriptorName>
<QualifierName UI="Q000472" MajorTopicYN="Y">pathogenicity</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045169" MajorTopicYN="N">Severe Acute Respiratory Syndrome</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
<QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D053676" MajorTopicYN="N">Syntenins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020798" MajorTopicYN="N">Two-Hybrid System Techniques</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014709" MajorTopicYN="N">Vero Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014759" MajorTopicYN="N">Viral Envelope Proteins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014774" MajorTopicYN="N">Virulence</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D048051" MajorTopicYN="N">p38 Mitogen-Activated Protein Kinases</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2013</Year>
<Month>12</Month>
<Day>10</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2014</Year>
<Month>07</Month>
<Day>08</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2014</Year>
<Month>8</Month>
<Day>15</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2014</Year>
<Month>8</Month>
<Day>15</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2015</Year>
<Month>12</Month>
<Day>22</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>epublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">25122212</ArticleId>
<ArticleId IdType="doi">10.1371/journal.ppat.1004320</ArticleId>
<ArticleId IdType="pii">PPATHOGENS-D-13-03246</ArticleId>
<ArticleId IdType="pmc">PMC4133396</ArticleId>
</ArticleIdList>
<ReferenceList><Reference><Citation>Virology. 2010 Jul 5;402(2):281-91</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20409569</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncogene. 2010 May 27;29(21):3054-66</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20228839</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biol Chem. 2001 Apr 6;276(14):10646-54</Citation>
<ArticleIdList><ArticleId IdType="pubmed">11152476</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>MBio. 2013;4(4). pii: e00271-13. doi: 10.1128/mBio.00271-13</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23919993</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Biochim Biophys Acta. 2013 Sep;1828(9):2026-31</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23688394</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Mol Biol. 2003 Aug 29;331(5):991-1004</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12927536</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2014 Jan;88(2):913-24</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24198408</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Virology. 2011 Jul 5;415(2):69-82</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21524776</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):14040-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16169905</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2008 Dec;4(12):e1000240</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19079579</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Biochem Biophys Res Commun. 1999 Oct 5;263(3):825-31</Citation>
<ArticleIdList><ArticleId IdType="pubmed">10512765</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Euro Surveill. 2012;17(40):20290</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23078800</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Protein Sci. 1997 Feb;6(2):464-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">9041651</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Lancet. 2003 May 24;361(9371):1767-72</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12781535</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2010 Apr;6(4):e1000849</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20386712</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Rev Drug Discov. 2003 Sep;2(9):717-26</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12951578</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2011 Oct;7(10):e1002315</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22028656</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2006 Nov;80(21):10900-6</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16928748</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>N Engl J Med. 2012 Nov 8;367(19):1814-20</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23075143</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Genome Res. 2005 Mar;15(3):376-84</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15710747</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2014 May;10(5):e1004077</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24788150</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Science. 2005 Oct 28;310(5748):676-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16195424</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Gen Virol. 2005 May;86(Pt 5):1423-34</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15831954</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Biophys J. 2006 Aug 1;91(3):938-47</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16698774</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2004 Jul;78(13):6723-34</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15194747</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2011 Nov;85(22):11544-56</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21775458</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Genet. 1997 Jul;16(3):277-82</Citation>
<ArticleIdList><ArticleId IdType="pubmed">9207794</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>FEBS J. 2012 Oct;279(19):3549-58</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22846345</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Virology. 2008 Jul 5;376(2):379-89</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18452964</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biol Chem. 2002 Feb 22;277(8):5699-702</Citation>
<ArticleIdList><ArticleId IdType="pubmed">11741967</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Immunol. 2004 Jun 15;172(12):7841-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15187168</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2012;8(5):e1002674</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22570613</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>FEBS Lett. 1995 May 8;364(2):229-33</Citation>
<ArticleIdList><ArticleId IdType="pubmed">7750577</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Gen Virol. 2005 Dec;86(Pt 12):3303-10</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16298975</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Stat Appl Genet Mol Biol. 2004;3:Article3</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16646809</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Biol Cell. 2001 Jul;12(7):1911-24</Citation>
<ArticleIdList><ArticleId IdType="pubmed">11451992</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Clin Chem. 2009 Apr;55(4):611-22</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19246619</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proteins. 2009 Dec;77(4):796-811</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19585657</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Virology. 2012 Oct 25;432(2):485-94</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22832120</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Emerg Infect Dis. 2007 Sep;13(9):1295-300</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18252098</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol Methods. 2013 Nov;193(2):639-46</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23911968</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>N Engl J Med. 2013 Aug 1;369(5):407-16</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23782161</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 1998 Oct;72(10):7885-94</Citation>
<ArticleIdList><ArticleId IdType="pubmed">9733825</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Biol Cell. 2010 Nov 15;21(22):3838-52</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20861307</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Virology. 2010 Mar 30;399(1):120-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20110095</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2007 Apr;81(7):3597-607</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17229680</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Res. 2007 Feb 15;67(4):1812-22</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17308124</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Virology. 2006 Jul 20;351(1):180-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16647731</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Lancet. 2003 May 24;361(9371):1773-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12781536</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2009 Nov;83(21):11385-90</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19710146</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2007 Jan;3(1):e5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17222058</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2007 Feb;81(4):1701-13</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17108030</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Protoc. 2009;4(1):44-57</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19131956</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biol Chem. 2014 Jan 3;289(1):13-27</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24189062</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>ACS Chem Biol. 2006 May 23;1(4):207-10</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17163673</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Cell Sci. 2001 Sep;114(Pt 18):3219-31</Citation>
<ArticleIdList><ArticleId IdType="pubmed">11591811</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Biochem J. 2011 Oct 15;439(2):195-205</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21954943</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>FEBS J. 2012 Oct;279(19):3529</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22748103</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Clin Chem. 2005 Dec;51(12):2333-40</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16195357</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Comput Biol. 2012;8(11):e1002749</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23133356</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Am J Physiol Lung Cell Mol Physiol. 2000 Nov;279(5):L895-902</Citation>
<ArticleIdList><ArticleId IdType="pubmed">11053025</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>N Engl J Med. 2003 Dec 18;349(25):2431-41</Citation>
<ArticleIdList><ArticleId IdType="pubmed">14681510</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2010 Feb;6(2):e1000756</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20140198</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Bioinformatics. 2003 Feb 12;19(3):368-75</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12584122</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2013 Jun;87(12):6551-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23576515</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Virol. 2009 Jul;83(14):7062-74</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19420084</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Virus Res. 2005 May;109(2):191-202</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15763150</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Espagne</li>
</country>
<region><li>Communauté de Madrid</li>
</region>
<settlement><li>Madrid</li>
</settlement>
<orgName><li>Université autonome de Madrid</li>
</orgName>
</list>
<tree><country name="Espagne"><region name="Communauté de Madrid"><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>
</region>
<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="Dediego, Marta L" sort="Dediego, Marta L" uniqKey="Dediego M" first="Marta L" last="Dediego">Marta L. Dediego</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="Nieto Torres, Jose L" sort="Nieto Torres, Jose L" uniqKey="Nieto Torres J" first="Jose L" last="Nieto-Torres">Jose L. Nieto-Torres</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>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/PubMed/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000F05 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd -nk 000F05 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= PubMed |étape= Checkpoint |type= RBID |clé= pubmed:25122212 |texte= The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/RBID.i -Sk "pubmed:25122212" \ | HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd \ | NlmPubMed2Wicri -a SrasV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |