The PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Is a Determinant of Viral Pathogenesis
Identifieur interne : 001549 ( Main/Exploration ); précédent : 001548; suivant : 001550The PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Is a Determinant of Viral Pathogenesis
Auteurs : Jose M. Jimenez-Guarde O ; Jose L. Nieto-Torres ; Marta L. Dediego ; Jose A. Regla-Nava ; Raul Fernandez-Delgado ; Carlos Casta O-Rodriguez ; Luis EnjuanesSource :
- PLoS Pathogens [ 1553-7366 ] ; 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
Url:
DOI: 10.1371/journal.ppat.1004320
PubMed: 25122212
PubMed Central: 4133396
Affiliations:
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Jimenez-Guarde O</name><affiliation><nlm:aff id="aff1"></nlm:aff></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><nlm:aff id="aff1"></nlm:aff></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><nlm:aff id="aff1"></nlm:aff></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><nlm:aff id="aff1"></nlm:aff></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><nlm:aff id="aff1"></nlm:aff></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><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Enjuanes, Luis" sort="Enjuanes, Luis" uniqKey="Enjuanes L" first="Luis" last="Enjuanes">Luis Enjuanes</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2014">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"><p>A recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) lacking the envelope (E) protein is attenuated <italic>in vivo</italic>. 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Stohr, K" uniqKey="Stohr K">K Stohr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Li, Ks" uniqKey="Li K">KS Li</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name></author><author><name sortKey="Tsoi, Hw" uniqKey="Tsoi H">HW 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Aarons</name></author><author><name sortKey="Tong, C" uniqKey="Tong C">C Tong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Assiri, A" uniqKey="Assiri A">A Assiri</name></author><author><name sortKey="Mcgeer, A" uniqKey="Mcgeer A">A McGeer</name></author><author><name sortKey="Perl, Tm" uniqKey="Perl T">TM Perl</name></author><author><name sortKey="Price, Cs" uniqKey="Price C">CS Price</name></author><author><name sortKey="Al Rabeeah, Aa" uniqKey="Al Rabeeah A">AA Al Rabeeah</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Torres, J" uniqKey="Torres J">J Torres</name></author><author><name sortKey="Parthasarathy, K" uniqKey="Parthasarathy K">K Parthasarathy</name></author><author><name sortKey="Lin, X" uniqKey="Lin X">X Lin</name></author><author><name sortKey="Saravanan, R" uniqKey="Saravanan R">R Saravanan</name></author><author><name sortKey="Liu, Dx" uniqKey="Liu D">DX Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Verdia Baguena, C" uniqKey="Verdia Baguena C">C Verdia-Baguena</name></author><author><name sortKey="Nieto Torres, Jl" uniqKey="Nieto Torres J">JL Nieto-Torres</name></author><author><name sortKey="Alcaraz, A" uniqKey="Alcaraz A">A Alcaraz</name></author><author><name sortKey="Dediego, Ml" uniqKey="Dediego M">ML Dediego</name></author><author><name sortKey="Torres, J" uniqKey="Torres J">J Torres</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Verdia Baguena, C" uniqKey="Verdia Baguena C">C Verdia-Baguena</name></author><author><name sortKey="Nieto Torres, Jl" uniqKey="Nieto Torres J">JL Nieto-Torres</name></author><author><name sortKey="Alcaraz, A" uniqKey="Alcaraz A">A Alcaraz</name></author><author><name sortKey="Dediego, Ml" uniqKey="Dediego M">ML Dediego</name></author><author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L 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Escors</name></author><author><name sortKey="Alvarez, E" uniqKey="Alvarez E">E Alvarez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snijder, Ej" uniqKey="Snijder E">EJ Snijder</name></author><author><name sortKey="Bredenbeek, Pj" uniqKey="Bredenbeek P">PJ Bredenbeek</name></author><author><name sortKey="Dobbe, Jc" uniqKey="Dobbe J">JC Dobbe</name></author><author><name sortKey="Thiel, V" uniqKey="Thiel V">V Thiel</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J Ziebuhr</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><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="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="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></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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