PandemieGrippaleV1, France, Analysis, bibRecord, 000498

PAR1 contributes to influenza A virus pathogenicity in mice

Identifieur interne : 000498 ( France/Analysis ); précédent : 000497; suivant : 000499

PAR1 contributes to influenza A virus pathogenicity in mice

Auteurs : Khaled Khoufache [France] ; Fatma Berri [France] ; Wolfgang Nacken [Allemagne] ; Annette B. Vogel [Allemagne] ; Marie Delenne [France] ; Eric Camerer [France] ; Shaun R. Coughlin [États-Unis] ; Peter Carmeliet [Belgique] ; Bruno Lina [France] ; Guus F. Rimmelzwaan [Pays-Bas] ; Oliver Planz [Allemagne] ; Stephan Ludwig [Allemagne] ; Beatrice Riteau [France]

Source :

Journal of Clinical Investigation [ 0021-9738 ] ; 2013.

RBID : Hal:hal-02643913

Descripteurs français

mix :
- INFECTION, INFLAMMATION, PANDEMIC INFLUENZA, PLASMINOGEN.

English descriptors

mix :
- ANTAGONIST VORAPAXAR, DEPENDENT PATHWAY, IN-VIVO, LUNG INJURY, PROTEASE-ACTIVATED RECEPTORS, THROMBIN.

Abstract

Influenza causes substantial morbidity and mortality, and highly pathogenic and drug-resistant strains are likely to emerge in the future. Protease-activated receptor 1 (PAR1) is a thrombin-activated receptor that contributes to inflammatory responses at mucosal surfaces. The role of PAR1 in pathogenesis of virus infections is unknown. Here, we demonstrate that PAR1 contributed to the deleterious inflammatory response after influenza virus infection in mice. Activating PAR1 by administering the agonist TFLLR-NH2 decreased survival and increased lung inflammation after influenza infection. Importantly, both administration of a PAR1 antagonist and PAR1 deficiency protected mice from infection with influenza A viruses (IAVs). Treatment with the PAR1 agonist did not alter survival of mice deficient in plasminogen (PLG), which suggests that PLG permits and/or interacts with a PAR1 function in this model. PARE antagonists are in human trials for other indications. Our findings suggest that PAR1 antagonism might be explored as a treatment for influenza, including that caused by highly pathogenic H5N1 and oseltamivir-resistant H1N1 viruses.

Url:

https://hal.inrae.fr/hal-02643913

DOI: 10.1172/JCI61667

Affiliations:

Links toward previous steps (curation, corpus...)

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Hal:hal-02643913

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en">PAR1 contributes to influenza A virus pathogenicity in mice</title>
<author><name sortKey="Khoufache, Khaled" sort="Khoufache, Khaled" uniqKey="Khoufache K" first="Khaled" last="Khoufache">Khaled Khoufache</name>
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              <country key="FR"></country>
            </address>
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          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
<placeName><settlement type="city">Tours</settlement>
<region type="old region" nuts="2">Région Centre</region>
<region type="region" nuts="2">Centre-Val de Loire</region>
</placeName>
<orgName type="university">Université de Tours</orgName>
<orgName type="institution" wicri:auto="newGroup">Centre Val de Loire Université</orgName>
</affiliation>
</author>
<author><name sortKey="Berri, Fatma" sort="Berri, Fatma" uniqKey="Berri F" first="Fatma" last="Berri">Fatma Berri</name>
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              <country key="FR"></country>
            </address>
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</placeName>
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</author>
<author><name sortKey="Nacken, Wolfgang" sort="Nacken, Wolfgang" uniqKey="Nacken W" first="Wolfgang" last="Nacken">Wolfgang Nacken</name>
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</affiliation>
</author>
<author><name sortKey="Vogel, Annette B" sort="Vogel, Annette B" uniqKey="Vogel A" first="Annette B." last="Vogel">Annette B. Vogel</name>
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          <orgName type="acronym">FLI</orgName>
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            </address>
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</affiliation>
</author>
<author><name sortKey="Delenne, Marie" sort="Delenne, Marie" uniqKey="Delenne M" first="Marie" last="Delenne">Marie Delenne</name>
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</tutelle>
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</hal:affiliation>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Coughlin, Shaun R" sort="Coughlin, Shaun R" uniqKey="Coughlin S" first="Shaun R." last="Coughlin">Shaun R. Coughlin</name>
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          <orgName type="acronym">UCSF</orgName>
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              <country key="US"></country>
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          <desc>            <address>              <country key="US"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Carmeliet, Peter" sort="Carmeliet, Peter" uniqKey="Carmeliet P" first="Peter" last="Carmeliet">Peter Carmeliet</name>
<affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-357456" status="INCOMING">          <orgName>Flanders Institute for Biotechnology</orgName>
          <desc>            <address>              <country key="BE"></country>
            </address>
          </desc>
        </hal:affiliation>
<country>Belgique</country>
</affiliation>
</author>
<author><name sortKey="Lina, Bruno" sort="Lina, Bruno" uniqKey="Lina B" first="Bruno" last="Lina">Bruno Lina</name>
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          <orgName>Virologie et pathologie humaine</orgName>
          <orgName type="acronym">VirPath</orgName>
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          <desc>            <address>              <country key="FR"></country>
            </address>
          </desc>
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          <orgName>Université Claude Bernard Lyon 1</orgName>
          <orgName type="acronym">UCBL</orgName>
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            </address>
            <ref type="url">http://www.univ-lyon1.fr/</ref>
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<tutelle active="#struct-301088" type="indirect"><org type="regroupinstitution" xml:id="struct-301088" status="VALID">          <orgName>Université de Lyon</orgName>
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              <country key="FR"></country>
            </address>
            <ref type="url">https://www.universite-lyon.fr/</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
<placeName><settlement type="city">Lyon</settlement>
<region type="region" nuts="2">Auvergne-Rhône-Alpes</region>
<region type="old region" nuts="2">Rhône-Alpes</region>
</placeName>
<orgName type="university">Université Claude Bernard Lyon 1</orgName>
<orgName type="institution" wicri:auto="newGroup">Université de Lyon</orgName>
</affiliation>
</author>
<author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name>
<affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-485122" status="VALID">          <orgName>Erasmus University Rotterdam</orgName>
          <date type="start">2017-02-16</date>
          <desc>            <address>              <country key="NL"></country>
            </address>
            <ref type="url">https://www.eur.nl/</ref>
          </desc>
        </hal:affiliation>
<country>Pays-Bas</country>
</affiliation>
</author>
<author><name sortKey="Planz, Oliver" sort="Planz, Oliver" uniqKey="Planz O" first="Oliver" last="Planz">Oliver Planz</name>
<affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-322700" status="VALID">          <orgName>Friedrich-Loeffler-Institut</orgName>
          <orgName type="acronym">FLI</orgName>
          <desc>            <address>              <addrLine>Federal Research Institute for Animal HealthSüdufer 10D-17493 Greifswald - Insel Riems</addrLine>
              <country key="DE"></country>
            </address>
            <ref type="url">https://www.fli.de</ref>
          </desc>
        </hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Ludwig, Stephan" sort="Ludwig, Stephan" uniqKey="Ludwig S" first="Stephan" last="Ludwig">Stephan Ludwig</name>
<affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-425052" status="VALID">          <orgName>University of Münster</orgName>
          <desc>            <address>              <addrLine>Universität Münster Schlossplatz 2 48149 Münster</addrLine>
              <country key="DE"></country>
            </address>
            <ref type="url">https://www.uni-muenster.de/de/</ref>
          </desc>
        </hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Riteau, Beatrice" sort="Riteau, Beatrice" uniqKey="Riteau B" first="Beatrice" last="Riteau">Beatrice Riteau</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-211885" status="OLD">          <orgName>Infectiologie Santé Publique</orgName>
          <orgName type="acronym">ISP-311</orgName>
          <date type="end">2019-12-31</date>
          <desc>            <address>              <addrLine>37380 Nouzilly</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">https://www6.val-de-loire.inra.fr/infectiologie-santepublique</ref>
          </desc>
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          <orgName type="acronym">INRA</orgName>
          <date type="start">1946-05-18</date>
          <date type="end">2019-12-31</date>
          <desc>            <address>              <country key="FR"></country>
            </address>
            <ref type="url">http://www.inra.fr</ref>
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<tutelle active="#struct-300298" type="direct"><org type="institution" xml:id="struct-300298" status="VALID">          <idno type="IdRef">026404478</idno>
          <orgName>Université de Tours</orgName>
          <date type="start">1970-12-17</date>
          <desc>            <address>              <addrLine>60 rue du Plat d'Étain, 37020 Tours cedex 1 </addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.univ-tours.fr</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
<placeName><settlement type="city">Tours</settlement>
<region type="old region" nuts="2">Région Centre</region>
<region type="region" nuts="2">Centre-Val de Loire</region>
</placeName>
<orgName type="university">Université de Tours</orgName>
<orgName type="institution" wicri:auto="newGroup">Centre Val de Loire Université</orgName>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.1172/JCI61667</idno>
<series><title level="j">Journal of Clinical Investigation</title>
<idno type="ISSN">0021-9738</idno>
<imprint><date type="datePub">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>ANTAGONIST VORAPAXAR</term>
<term>DEPENDENT PATHWAY</term>
<term>IN-VIVO</term>
<term>LUNG INJURY</term>
<term>PROTEASE-ACTIVATED RECEPTORS</term>
<term>THROMBIN</term>
</keywords>
<keywords scheme="mix" xml:lang="fr"><term>INFECTION</term>
<term>INFLAMMATION</term>
<term>PANDEMIC INFLUENZA</term>
<term>PLASMINOGEN</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">              <p>Influenza causes substantial morbidity and mortality, and highly pathogenic and drug-resistant strains are likely to emerge in the future. Protease-activated receptor 1 (PAR1) is a thrombin-activated receptor that contributes to inflammatory responses at mucosal surfaces. The role of PAR1 in pathogenesis of virus infections is unknown. Here, we demonstrate that PAR1 contributed to the deleterious inflammatory response after influenza virus infection in mice. Activating PAR1 by administering the agonist TFLLR-NH2 decreased survival and increased lung inflammation after influenza infection. Importantly, both administration of a PAR1 antagonist and PAR1 deficiency protected mice from infection with influenza A viruses (IAVs). Treatment with the PAR1 agonist did not alter survival of mice deficient in plasminogen (PLG), which suggests that PLG permits and/or interacts with a PAR1 function in this model. PARE antagonists are in human trials for other indications. Our findings suggest that PAR1 antagonism might be explored as a treatment for influenza, including that caused by highly pathogenic H5N1 and oseltamivir-resistant H1N1 viruses.</p>
            </div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Belgique</li>
<li>France</li>
<li>Pays-Bas</li>
<li>États-Unis</li>
</country>
<region><li>Auvergne-Rhône-Alpes</li>
<li>Centre-Val de Loire</li>
<li>Rhône-Alpes</li>
<li>Région Centre</li>
</region>
<settlement><li>Lyon</li>
<li>Tours</li>
</settlement>
<orgName><li>Centre Val de Loire Université</li>
<li>Université Claude Bernard Lyon 1</li>
<li>Université de Lyon</li>
<li>Université de Tours</li>
</orgName>
</list>
<tree><country name="France"><region name="Région Centre"><name sortKey="Khoufache, Khaled" sort="Khoufache, Khaled" uniqKey="Khoufache K" first="Khaled" last="Khoufache">Khaled Khoufache</name>
</region>
<name sortKey="Berri, Fatma" sort="Berri, Fatma" uniqKey="Berri F" first="Fatma" last="Berri">Fatma Berri</name>
<name sortKey="Camerer, Eric" sort="Camerer, Eric" uniqKey="Camerer E" first="Eric" last="Camerer">Eric Camerer</name>
<name sortKey="Delenne, Marie" sort="Delenne, Marie" uniqKey="Delenne M" first="Marie" last="Delenne">Marie Delenne</name>
<name sortKey="Lina, Bruno" sort="Lina, Bruno" uniqKey="Lina B" first="Bruno" last="Lina">Bruno Lina</name>
<name sortKey="Riteau, Beatrice" sort="Riteau, Beatrice" uniqKey="Riteau B" first="Beatrice" last="Riteau">Beatrice Riteau</name>
</country>
<country name="Allemagne"><noRegion><name sortKey="Nacken, Wolfgang" sort="Nacken, Wolfgang" uniqKey="Nacken W" first="Wolfgang" last="Nacken">Wolfgang Nacken</name>
</noRegion>
<name sortKey="Ludwig, Stephan" sort="Ludwig, Stephan" uniqKey="Ludwig S" first="Stephan" last="Ludwig">Stephan Ludwig</name>
<name sortKey="Planz, Oliver" sort="Planz, Oliver" uniqKey="Planz O" first="Oliver" last="Planz">Oliver Planz</name>
<name sortKey="Vogel, Annette B" sort="Vogel, Annette B" uniqKey="Vogel A" first="Annette B." last="Vogel">Annette B. Vogel</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Coughlin, Shaun R" sort="Coughlin, Shaun R" uniqKey="Coughlin S" first="Shaun R." last="Coughlin">Shaun R. Coughlin</name>
</noRegion>
</country>
<country name="Belgique"><noRegion><name sortKey="Carmeliet, Peter" sort="Carmeliet, Peter" uniqKey="Carmeliet P" first="Peter" last="Carmeliet">Peter Carmeliet</name>
</noRegion>
</country>
<country name="Pays-Bas"><noRegion><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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{{Explor lien
   |wiki=    Sante
   |area=    PandemieGrippaleV1
   |flux=    France
   |étape=   Analysis
   |type=    RBID
   |clé=     Hal:hal-02643913
   |texte=   PAR1 contributes to influenza A virus pathogenicity in mice
}}

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	Serveur d'exploration sur les pandémies grippales
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PAR1 contributes to influenza A virus pathogenicity in mice

PAR1 contributes to influenza A virus pathogenicity in mice

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