Pandemic Influenza A Viruses Escape from Restriction by Human MxA through Adaptive Mutations in the Nucleoprotein
Identifieur interne : 000854 ( Main/Exploration ); précédent : 000853; suivant : 000855Pandemic Influenza A Viruses Escape from Restriction by Human MxA through Adaptive Mutations in the Nucleoprotein
Auteurs : Benjamin M Nz [Allemagne] ; Dominik Dornfeld [Allemagne] ; Veronika Götz [Allemagne] ; Roland Zell [Allemagne] ; Petra Zimmermann [Allemagne] ; Otto Haller [Allemagne] ; Georg Kochs [Allemagne] ; Martin Schwemmle [Allemagne]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2013.
Abstract
The interferon-induced dynamin-like MxA GTPase restricts the replication of influenza A viruses. We identified adaptive mutations in the nucleoprotein (NP) of pandemic strains A/Brevig Mission/1/1918 (1918) and A/Hamburg/4/2009 (pH1N1) that confer MxA resistance. These resistance-associated amino acids in NP differ between the two strains but form a similar discrete surface-exposed cluster in the body domain of NP, indicating that MxA resistance evolved independently. The 1918 cluster was conserved in all descendent strains of seasonal influenza viruses. Introduction of this cluster into the NP of the MxA-sensitive influenza virus A/Thailand/1(KAN-1)/04 (H5N1) resulted in a gain of MxA resistance coupled with a decrease in viral replication fitness. Conversely, introduction of MxA-sensitive amino acids into pH1N1 NP enhanced viral growth in Mx-negative cells. We conclude that human MxA represents a barrier against zoonotic introduction of avian influenza viruses and that adaptive mutations in the viral NP should be carefully monitored.
Url:
DOI: 10.1371/journal.ppat.1003279
PubMed: 23555271
PubMed Central: 3610643
Affiliations:
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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="Dornfeld, Dominik" sort="Dornfeld, Dominik" uniqKey="Dornfeld D" first="Dominik" last="Dornfeld">Dominik Dornfeld</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, 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="Gotz, Veronika" sort="Gotz, Veronika" uniqKey="Gotz V" first="Veronika" last="Götz">Veronika Götz</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, 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="Zell, Roland" sort="Zell, Roland" uniqKey="Zell R" first="Roland" last="Zell">Roland Zell</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Institute of Virology und Antiviral Therapy, Universitätsklinikum Jena, Friedrich Schiller University Jena, Jena, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Virology und Antiviral Therapy, Universitätsklinikum Jena, Friedrich Schiller University Jena, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Zimmermann, Petra" sort="Zimmermann, Petra" uniqKey="Zimmermann P" first="Petra" last="Zimmermann">Petra Zimmermann</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, 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="Haller, Otto" sort="Haller, Otto" uniqKey="Haller O" first="Otto" last="Haller">Otto Haller</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, 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="Kochs, Georg" sort="Kochs, Georg" uniqKey="Kochs G" first="Georg" last="Kochs">Georg Kochs</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, 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="Schwemmle, Martin" sort="Schwemmle, Martin" uniqKey="Schwemmle M" first="Martin" last="Schwemmle">Martin Schwemmle</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, 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></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The interferon-induced dynamin-like MxA GTPase restricts the replication of influenza A viruses. We identified adaptive mutations in the nucleoprotein (NP) of pandemic strains A/Brevig Mission/1/1918 (1918) and A/Hamburg/4/2009 (pH1N1) that confer MxA resistance. These resistance-associated amino acids in NP differ between the two strains but form a similar discrete surface-exposed cluster in the body domain of NP, indicating that MxA resistance evolved independently. The 1918 cluster was conserved in all descendent strains of seasonal influenza viruses. Introduction of this cluster into the NP of the MxA-sensitive influenza virus A/Thailand/1(KAN-1)/04 (H5N1) resulted in a gain of MxA resistance coupled with a decrease in viral replication fitness. Conversely, introduction of MxA-sensitive amino acids into pH1N1 NP enhanced viral growth in Mx-negative cells. We conclude that human MxA represents a barrier against zoonotic introduction of avian influenza viruses and that adaptive mutations in the viral NP should be carefully monitored.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author><author><name sortKey="Schneeberger, Pm" uniqKey="Schneeberger P">PM Schneeberger</name></author><author><name sortKey="Rozendaal, Fw" uniqKey="Rozendaal F">FW Rozendaal</name></author><author><name sortKey="Broekman, Jm" uniqKey="Broekman J">JM Broekman</name></author><author><name sortKey="Kemink, Sa" uniqKey="Kemink S">SA Kemink</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tweed, Sa" uniqKey="Tweed S">SA Tweed</name></author><author><name sortKey="Skowronski, Dm" uniqKey="Skowronski D">DM Skowronski</name></author><author><name sortKey="David, St" uniqKey="David S">ST David</name></author><author><name 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sortKey="Ponten, A" uniqKey="Ponten A">A Ponten</name></author><author><name sortKey="Sick, C" uniqKey="Sick C">C Sick</name></author><author><name sortKey="Weeber, M" uniqKey="Weeber M">M Weeber</name></author><author><name sortKey="Haller, O" uniqKey="Haller O">O Haller</name></author><author><name sortKey="Kochs, G" uniqKey="Kochs G">G Kochs</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>Bade-Wurtemberg</li><li>District de Fribourg-en-Brisgau</li></region><settlement><li>Fribourg-en-Brisgau</li></settlement></list><tree><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="M Nz, Benjamin" sort="M Nz, Benjamin" uniqKey="M Nz B" first="Benjamin" last="M Nz">Benjamin M Nz</name></region><name sortKey="Dornfeld, Dominik" sort="Dornfeld, Dominik" uniqKey="Dornfeld D" first="Dominik" last="Dornfeld">Dominik Dornfeld</name><name sortKey="Gotz, Veronika" sort="Gotz, Veronika" uniqKey="Gotz V" first="Veronika" last="Götz">Veronika Götz</name><name sortKey="Haller, Otto" sort="Haller, Otto" uniqKey="Haller O" first="Otto" last="Haller">Otto Haller</name><name sortKey="Kochs, Georg" sort="Kochs, Georg" uniqKey="Kochs G" first="Georg" last="Kochs">Georg Kochs</name><name sortKey="Schwemmle, Martin" sort="Schwemmle, Martin" uniqKey="Schwemmle M" first="Martin" last="Schwemmle">Martin Schwemmle</name><name sortKey="Zell, Roland" sort="Zell, Roland" uniqKey="Zell R" first="Roland" last="Zell">Roland Zell</name><name sortKey="Zimmermann, Petra" sort="Zimmermann, Petra" uniqKey="Zimmermann P" first="Petra" last="Zimmermann">Petra Zimmermann</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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