WeightNameValue
1000 Titel
  • Effects of allelic variations in the human myxovirus resistance protein A on its antiviral activity
1000 Autor/in
  1. Graf, Laura |
  2. Dick, Alexey |
  3. Sendker, Franziska |
  4. Barth, Emanuel |
  5. Marz, Manja |
  6. Daumke, Oliver |
  7. Kochs, Georg |
1000 Erscheinungsjahr 2018
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2018-01-12
1000 Erschienen in
1000 Quellenangabe
  • 293(9):3056-3072
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29330299/ |
  • https://dx.doi.org/10.1074/jbc.M117.812784 |
1000 Ergänzendes Material
  • http://www.jbc.org/content/293/9/3056/suppl/DC1 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Only a minority of patients infected with seasonal influenza A viruses exhibit a severe or fatal outcome of infection, but the reasons for this inter-individual variability in influenza susceptibility are unclear. To gain further insights into the molecular mechanisms underlying this variability, we investigated naturally occurring allelic variations of the myxovirus resistance 1 (MX1) gene coding for the influenza restriction factor MxA. The interferon-induced dynamin-like GTPase consists of an N-terminal GTPase domain, a bundle signaling element, and a C-terminal stalk responsible for oligomerization and viral target recognition. We used online databases to search for variations in the MX1 gene. Deploying in vitro approaches, we found that non-synonymous variations in the GTPase domain cause the loss of antiviral and enzymatic activities. Furthermore, we showed that these amino acid substitutions disrupt the interface for GTPase domain dimerization required for the stimulation of GTP hydrolysis. Variations in the stalk were neutral or slightly enhanced or abolished MxA antiviral function. Remarkably, two other stalk variants altered MxA's antiviral specificity. Variations causing the loss of antiviral activity were found only in heterozygous carriers. Interestingly, the inactive stalk variants blocked the antiviral activity of WT MxA in a dominant-negative way, suggesting that heterozygotes are phenotypically MxA-negative. In contrast, the GTPase-deficient variants showed no dominant-negative effect, indicating that heterozygous carriers should remain unaffected. Our results demonstrate that naturally occurring mutations in the human MX1 gene can influence MxA function, which may explain individual variations in influenza virus susceptibility in the human population.
1000 Sacherschließung
lokal allelic variations
lokal Mx proteins
lokal genetic polymorphism
lokal antiviral response
lokal dynamin
lokal interferon
lokal innate immunity
lokal influenza virus
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/R3JhZiwgTGF1cmE=|https://frl.publisso.de/adhoc/uri/RGljaywgQWxleGV5|https://frl.publisso.de/adhoc/uri/U2VuZGtlciwgRnJhbnppc2th|https://frl.publisso.de/adhoc/uri/QmFydGgsIEVtYW51ZWw=|https://frl.publisso.de/adhoc/uri/TWFyeiwgTWFuamE=|https://frl.publisso.de/adhoc/uri/RGF1bWtlLCBPbGl2ZXI=|https://orcid.org/0000-0003-0187-559X
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
  2. Thüringer Ministerium für Wirtschaft, Wissenschaft und Digitale Gesellschaft |
1000 Fördernummer
  1. KO 1579/8-2; DA 1127/1; MA 5082/7-1
  2. RegenerAging–FSU-I-03/14
1000 Förderprogramm
  1. -
  2. ProExzellenz
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer KO 1579/8-2; DA 1127/1; MA 5082/7-1
  2. 1000 joinedFunding-child
    1000 Förderer Thüringer Ministerium für Wirtschaft, Wissenschaft und Digitale Gesellschaft |
    1000 Förderprogramm ProExzellenz
    1000 Fördernummer RegenerAging–FSU-I-03/14
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6414508.rdf
1000 Erstellt am 2019-05-17T10:33:29.346+0200
1000 Erstellt von 285
1000 beschreibt frl:6414508
1000 Bearbeitet von 122
1000 Zuletzt bearbeitet Tue May 28 13:10:09 CEST 2019
1000 Objekt bearb. Tue May 28 13:10:09 CEST 2019
1000 Vgl. frl:6414508
1000 Oai Id
  1. oai:frl.publisso.de:frl:6414508 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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