Multiple Anti-Interferon Actions of the Influenza A Virus NS1 Protein▿
Identifieur interne : 000509 ( Ncbi/Merge ); précédent : 000508; suivant : 000510Multiple Anti-Interferon Actions of the Influenza A Virus NS1 Protein▿
Auteurs : Georg Kochs ; Adolfo García-Sastre ; Luis Martínez-SobridoSource :
- Journal of Virology [ 0022-538X ] ; 2007.
Descripteurs français
- KwdFr :
- Animaux, Cellules Vero, Facteur de spécificité de clivage et polyadénylation (immunologie), Facteur-3 de régulation d'interféron (immunologie), Facteur-3 de régulation d'interféron (métabolisme), Facteurs de régulation d'interféron (immunologie), Facteurs de régulation d'interféron (métabolisme), Flambées de maladies, Grippe humaine (immunologie), Grippe humaine (métabolisme), Grippe humaine (épidémiologie), Humains, Interféron alpha (antagonistes et inhibiteurs), Interféron alpha (biosynthèse), Interféron alpha (immunologie), Interféron bêta (antagonistes et inhibiteurs), Interféron bêta (biosynthèse), Interféron bêta (immunologie), Mutation faux-sens, Poulets, Protéines aviaires (immunologie), Protéines aviaires (métabolisme), Protéines virales non structurales (immunologie), Protéines virales non structurales (métabolisme), Précurseurs des ARN (biosynthèse), Précurseurs des ARN (immunologie), Régulation négative (immunologie), Sous-type H1N1 du virus de la grippe A (immunologie), Sous-type H1N1 du virus de la grippe A (métabolisme), Sous-type H1N1 du virus de la grippe A (pathogénicité), Spécificité d'espèce, Structure tertiaire des protéines, Substitution d'acide aminé.
- MESH :
- antagonistes et inhibiteurs : Interféron alpha, Interféron bêta.
- biosynthèse : Interféron alpha, Interféron bêta, Précurseurs des ARN.
- immunologie : Facteur de spécificité de clivage et polyadénylation, Facteur-3 de régulation d'interféron, Facteurs de régulation d'interféron, Grippe humaine, Interféron alpha, Interféron bêta, Protéines aviaires, Protéines virales non structurales, Précurseurs des ARN, Régulation négative, Sous-type H1N1 du virus de la grippe A.
- métabolisme : Facteur-3 de régulation d'interféron, Facteurs de régulation d'interféron, Grippe humaine, Protéines aviaires, Protéines virales non structurales, Sous-type H1N1 du virus de la grippe A.
- pathogénicité : Sous-type H1N1 du virus de la grippe A.
- épidémiologie : Grippe humaine.
- Animaux, Cellules Vero, Flambées de maladies, Humains, Mutation faux-sens, Poulets, Spécificité d'espèce, Structure tertiaire des protéines, Substitution d'acide aminé.
English descriptors
- KwdEn :
- Amino Acid Substitution, Animals, Avian Proteins (immunology), Avian Proteins (metabolism), Chickens, Chlorocebus aethiops, Cleavage And Polyadenylation Specificity Factor (immunology), Disease Outbreaks, Down-Regulation (immunology), Humans, Influenza A Virus, H1N1 Subtype (immunology), Influenza A Virus, H1N1 Subtype (metabolism), Influenza A Virus, H1N1 Subtype (pathogenicity), Influenza, Human (epidemiology), Influenza, Human (immunology), Influenza, Human (metabolism), Interferon Regulatory Factor-3 (immunology), Interferon Regulatory Factor-3 (metabolism), Interferon Regulatory Factors (immunology), Interferon Regulatory Factors (metabolism), Interferon-alpha (antagonists & inhibitors), Interferon-alpha (biosynthesis), Interferon-alpha (immunology), Interferon-beta (antagonists & inhibitors), Interferon-beta (biosynthesis), Interferon-beta (immunology), Mutation, Missense, Protein Structure, Tertiary, RNA Precursors (biosynthesis), RNA Precursors (immunology), Species Specificity, Vero Cells, Viral Nonstructural Proteins (immunology), Viral Nonstructural Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Interferon-alpha, Interferon-beta.
- chemical , biosynthesis : Interferon-alpha, Interferon-beta, RNA Precursors.
- chemical , immunology : Avian Proteins, Cleavage And Polyadenylation Specificity Factor, Interferon Regulatory Factor-3, Interferon Regulatory Factors, Interferon-alpha, Interferon-beta, RNA Precursors, Viral Nonstructural Proteins.
- chemical , metabolism : Avian Proteins, Interferon Regulatory Factor-3, Interferon Regulatory Factors, Viral Nonstructural Proteins.
- epidemiology : Influenza, Human.
- immunology : Down-Regulation, Influenza A Virus, H1N1 Subtype, Influenza, Human.
- metabolism : Influenza A Virus, H1N1 Subtype, Influenza, Human.
- pathogenicity : Influenza A Virus, H1N1 Subtype.
- Amino Acid Substitution, Animals, Chickens, Chlorocebus aethiops, Disease Outbreaks, Humans, Mutation, Missense, Protein Structure, Tertiary, Species Specificity, Vero Cells.
Abstract
The replication and pathogenicity of influenza A virus (FLUAV) are controlled in part by the alpha/beta interferon (IFN-α/β) system. This virus-host interplay is dependent on the production of IFN-α/β and on the capacity of the viral nonstructural protein NS1 to counteract the IFN system. Two different mechanisms have been described for NS1, namely, blocking the activation of IFN regulatory factor 3 (IRF3) and blocking posttranscriptional processing of cellular mRNAs. Here we directly compare the abilities of NS1 gene products from three different human FLUAV (H1N1) strains to counteract the antiviral host response. We found that A/PR/8/34 NS1 has a strong capacity to inhibit IRF3 and activation of the IFN-β promoter but is unable to suppress expression of other cellular genes. In contrast, the NS1 proteins of A/Tx/36/91 and of A/BM/1/18, the virus that caused the Spanish influenza pandemic, caused suppression of additional cellular gene expression. Thus, these NS1 proteins prevented the establishment of an IFN-induced antiviral state, allowing virus replication even in the presence of IFN. Interestingly, the block in gene expression was dependent on a newly described NS1 domain that is important for interaction with the cleavage and polyadenylation specificity factor (CPSF) component of the cellular pre-mRNA processing machinery but is not functional in A/PR/8/34 NS1. We identified the Phe-103 and Met-106 residues in NS1 as being critical for CPSF binding, together with the previously described C-terminal binding domain. Our results demonstrate the capacity of FLUAV NS1 to suppress the antiviral host defense at multiple levels and the existence of strain-specific differences that may modulate virus pathogenicity.
Url:
DOI: 10.1128/JVI.02581-06
PubMed: 17442719
PubMed Central: 1933316
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PMC:1933316Le document en format XML
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Vero</term><term>Flambées de maladies</term><term>Humains</term><term>Mutation faux-sens</term><term>Poulets</term><term>Spécificité d'espèce</term><term>Structure tertiaire des protéines</term><term>Substitution d'acide aminé</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The replication and pathogenicity of influenza A virus (FLUAV) are controlled in part by the alpha/beta interferon (IFN-α/β) system. This virus-host interplay is dependent on the production of IFN-α/β and on the capacity of the viral nonstructural protein NS1 to counteract the IFN system. Two different mechanisms have been described for NS1, namely, blocking the activation of IFN regulatory factor 3 (IRF3) and blocking posttranscriptional processing of cellular mRNAs. Here we directly compare the abilities of NS1 gene products from three different human FLUAV (H1N1) strains to counteract the antiviral host response. We found that A/PR/8/34 NS1 has a strong capacity to inhibit IRF3 and activation of the IFN-β promoter but is unable to suppress expression of other cellular genes. In contrast, the NS1 proteins of A/Tx/36/91 and of A/BM/1/18, the virus that caused the Spanish influenza pandemic, caused suppression of additional cellular gene expression. Thus, these NS1 proteins prevented the establishment of an IFN-induced antiviral state, allowing virus replication even in the presence of IFN. Interestingly, the block in gene expression was dependent on a newly described NS1 domain that is important for interaction with the cleavage and polyadenylation specificity factor (CPSF) component of the cellular pre-mRNA processing machinery but is not functional in A/PR/8/34 NS1. We identified the Phe-103 and Met-106 residues in NS1 as being critical for CPSF binding, together with the previously described C-terminal binding domain. Our results demonstrate the capacity of FLUAV NS1 to suppress the antiviral host defense at multiple levels and the existence of strain-specific differences that may modulate virus pathogenicity.</p></div></front></TEI><double pmid="17442719"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Multiple Anti-Interferon Actions of the Influenza A Virus NS1 Protein<xref ref-type="fn" rid="fn2">▿</xref> </title><author><name sortKey="Kochs, Georg" sort="Kochs, Georg" uniqKey="Kochs G" first="Georg" last="Kochs">Georg Kochs</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martínez-Sobrido">Luis Martínez-Sobrido</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17442719</idno><idno type="pmc">1933316</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933316</idno><idno type="RBID">PMC:1933316</idno><idno type="doi">10.1128/JVI.02581-06</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">000348</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000348</idno><idno type="wicri:Area/Pmc/Curation">000348</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000348</idno><idno type="wicri:Area/Pmc/Checkpoint">000D77</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000D77</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Multiple Anti-Interferon Actions of the Influenza A Virus NS1 Protein<xref ref-type="fn" rid="fn2">▿</xref> </title><author><name sortKey="Kochs, Georg" sort="Kochs, Georg" uniqKey="Kochs G" first="Georg" last="Kochs">Georg Kochs</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martínez-Sobrido">Luis Martínez-Sobrido</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The replication and pathogenicity of influenza A virus (FLUAV) are controlled in part by the alpha/beta interferon (IFN-α/β) system. This virus-host interplay is dependent on the production of IFN-α/β and on the capacity of the viral nonstructural protein NS1 to counteract the IFN system. Two different mechanisms have been described for NS1, namely, blocking the activation of IFN regulatory factor 3 (IRF3) and blocking posttranscriptional processing of cellular mRNAs. Here we directly compare the abilities of NS1 gene products from three different human FLUAV (H1N1) strains to counteract the antiviral host response. We found that A/PR/8/34 NS1 has a strong capacity to inhibit IRF3 and activation of the IFN-β promoter but is unable to suppress expression of other cellular genes. In contrast, the NS1 proteins of A/Tx/36/91 and of A/BM/1/18, the virus that caused the Spanish influenza pandemic, caused suppression of additional cellular gene expression. Thus, these NS1 proteins prevented the establishment of an IFN-induced antiviral state, allowing virus replication even in the presence of IFN. Interestingly, the block in gene expression was dependent on a newly described NS1 domain that is important for interaction with the cleavage and polyadenylation specificity factor (CPSF) component of the cellular pre-mRNA processing machinery but is not functional in A/PR/8/34 NS1. We identified the Phe-103 and Met-106 residues in NS1 as being critical for CPSF binding, together with the previously described C-terminal binding domain. Our results demonstrate the capacity of FLUAV NS1 to suppress the antiviral host defense at multiple levels and the existence of strain-specific differences that may modulate virus pathogenicity.</p></div></front></TEI></pmc><pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Multiple anti-interferon actions of the influenza A virus NS1 protein.</title><author><name sortKey="Kochs, Georg" sort="Kochs, Georg" uniqKey="Kochs G" first="Georg" last="Kochs">Georg Kochs</name><affiliation wicri:level="3"><nlm:affiliation>Department of Virology, University of Freiburg, D-79008 Freiburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Virology, University of Freiburg, D-79008 Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name></author><author><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martínez-Sobrido">Luis Martínez-Sobrido</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2007">2007</date><idno type="RBID">pubmed:17442719</idno><idno type="pmid">17442719</idno><idno type="doi">10.1128/JVI.02581-06</idno><idno type="wicri:Area/PubMed/Corpus">001B47</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001B47</idno><idno type="wicri:Area/PubMed/Curation">001B47</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001B47</idno><idno type="wicri:Area/PubMed/Checkpoint">001940</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001940</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Multiple anti-interferon actions of the influenza A virus NS1 protein.</title><author><name sortKey="Kochs, Georg" sort="Kochs, Georg" uniqKey="Kochs G" first="Georg" last="Kochs">Georg Kochs</name><affiliation wicri:level="3"><nlm:affiliation>Department of Virology, University of Freiburg, D-79008 Freiburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Virology, University of Freiburg, D-79008 Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name></author><author><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martínez-Sobrido">Luis Martínez-Sobrido</name></author></analytic><series><title level="j">Journal of virology</title><idno type="ISSN">0022-538X</idno><imprint><date when="2007" type="published">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Substitution</term><term>Animals</term><term>Avian Proteins (immunology)</term><term>Avian Proteins (metabolism)</term><term>Chickens</term><term>Chlorocebus aethiops</term><term>Cleavage And Polyadenylation Specificity Factor (immunology)</term><term>Disease Outbreaks</term><term>Down-Regulation (immunology)</term><term>Humans</term><term>Influenza A Virus, H1N1 Subtype (immunology)</term><term>Influenza A Virus, H1N1 Subtype (metabolism)</term><term>Influenza A Virus, H1N1 Subtype (pathogenicity)</term><term>Influenza, Human (epidemiology)</term><term>Influenza, Human (immunology)</term><term>Influenza, Human (metabolism)</term><term>Interferon Regulatory Factor-3 (immunology)</term><term>Interferon Regulatory Factor-3 (metabolism)</term><term>Interferon Regulatory Factors (immunology)</term><term>Interferon Regulatory Factors (metabolism)</term><term>Interferon-alpha (antagonists & inhibitors)</term><term>Interferon-alpha (biosynthesis)</term><term>Interferon-alpha (immunology)</term><term>Interferon-beta (antagonists & inhibitors)</term><term>Interferon-beta (biosynthesis)</term><term>Interferon-beta (immunology)</term><term>Mutation, Missense</term><term>Protein Structure, Tertiary</term><term>RNA Precursors (biosynthesis)</term><term>RNA Precursors (immunology)</term><term>Species Specificity</term><term>Vero Cells</term><term>Viral Nonstructural Proteins (immunology)</term><term>Viral Nonstructural Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Facteur de spécificité de clivage et polyadénylation (immunologie)</term><term>Facteur-3 de régulation d'interféron (immunologie)</term><term>Facteur-3 de régulation d'interféron (métabolisme)</term><term>Facteurs de régulation d'interféron (immunologie)</term><term>Facteurs de régulation d'interféron (métabolisme)</term><term>Flambées de maladies</term><term>Grippe humaine (immunologie)</term><term>Grippe humaine (métabolisme)</term><term>Grippe humaine (épidémiologie)</term><term>Humains</term><term>Interféron alpha (antagonistes et inhibiteurs)</term><term>Interféron alpha (biosynthèse)</term><term>Interféron alpha (immunologie)</term><term>Interféron bêta (antagonistes et inhibiteurs)</term><term>Interféron bêta (biosynthèse)</term><term>Interféron bêta (immunologie)</term><term>Mutation faux-sens</term><term>Poulets</term><term>Protéines aviaires (immunologie)</term><term>Protéines aviaires (métabolisme)</term><term>Protéines virales non structurales (immunologie)</term><term>Protéines virales non structurales (métabolisme)</term><term>Précurseurs des ARN (biosynthèse)</term><term>Précurseurs des ARN (immunologie)</term><term>Régulation négative (immunologie)</term><term>Sous-type H1N1 du virus de la grippe A (immunologie)</term><term>Sous-type H1N1 du virus de la grippe A (métabolisme)</term><term>Sous-type H1N1 du virus de la grippe A (pathogénicité)</term><term>Spécificité d'espèce</term><term>Structure tertiaire des protéines</term><term>Substitution d'acide aminé</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Interferon-alpha</term><term>Interferon-beta</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Interferon-alpha</term><term>Interferon-beta</term><term>RNA Precursors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Avian Proteins</term><term>Cleavage And Polyadenylation Specificity Factor</term><term>Interferon Regulatory Factor-3</term><term>Interferon Regulatory Factors</term><term>Interferon-alpha</term><term>Interferon-beta</term><term>RNA Precursors</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Avian Proteins</term><term>Interferon Regulatory Factor-3</term><term>Interferon Regulatory Factors</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Interféron alpha</term><term>Interféron bêta</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Interféron alpha</term><term>Interféron bêta</term><term>Précurseurs des ARN</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Facteur de spécificité de clivage et polyadénylation</term><term>Facteur-3 de régulation d'interféron</term><term>Facteurs de régulation d'interféron</term><term>Grippe humaine</term><term>Interféron alpha</term><term>Interféron bêta</term><term>Protéines aviaires</term><term>Protéines virales non structurales</term><term>Précurseurs des ARN</term><term>Régulation négative</term><term>Sous-type H1N1 du virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Down-Regulation</term><term>Influenza A Virus, H1N1 Subtype</term><term>Influenza, Human</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term><term>Influenza, Human</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur-3 de régulation d'interféron</term><term>Facteurs de régulation d'interféron</term><term>Grippe humaine</term><term>Protéines aviaires</term><term>Protéines virales non structurales</term><term>Sous-type H1N1 du virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Sous-type H1N1 du virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr"><term>Grippe humaine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Substitution</term><term>Animals</term><term>Chickens</term><term>Chlorocebus aethiops</term><term>Disease Outbreaks</term><term>Humans</term><term>Mutation, Missense</term><term>Protein Structure, Tertiary</term><term>Species Specificity</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Flambées de maladies</term><term>Humains</term><term>Mutation faux-sens</term><term>Poulets</term><term>Spécificité d'espèce</term><term>Structure tertiaire des protéines</term><term>Substitution d'acide aminé</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The replication and pathogenicity of influenza A virus (FLUAV) are controlled in part by the alpha/beta interferon (IFN-alpha/beta) system. This virus-host interplay is dependent on the production of IFN-alpha/beta and on the capacity of the viral nonstructural protein NS1 to counteract the IFN system. Two different mechanisms have been described for NS1, namely, blocking the activation of IFN regulatory factor 3 (IRF3) and blocking posttranscriptional processing of cellular mRNAs. Here we directly compare the abilities of NS1 gene products from three different human FLUAV (H1N1) strains to counteract the antiviral host response. We found that A/PR/8/34 NS1 has a strong capacity to inhibit IRF3 and activation of the IFN-beta promoter but is unable to suppress expression of other cellular genes. In contrast, the NS1 proteins of A/Tx/36/91 and of A/BM/1/18, the virus that caused the Spanish influenza pandemic, caused suppression of additional cellular gene expression. Thus, these NS1 proteins prevented the establishment of an IFN-induced antiviral state, allowing virus replication even in the presence of IFN. Interestingly, the block in gene expression was dependent on a newly described NS1 domain that is important for interaction with the cleavage and polyadenylation specificity factor (CPSF) component of the cellular pre-mRNA processing machinery but is not functional in A/PR/8/34 NS1. We identified the Phe-103 and Met-106 residues in NS1 as being critical for CPSF binding, together with the previously described C-terminal binding domain. Our results demonstrate the capacity of FLUAV NS1 to suppress the antiviral host defense at multiple levels and the existence of strain-specific differences that may modulate virus pathogenicity.</div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
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