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2011-11-18Zeitschriftenartikel DOI: 10.1093/infdis/jir716
Synergistic Adaptive Mutations in the Hemagglutinin and Polymerase Acidic Protein Lead to Increased Virulence of Pandemic 2009 H1N1 Influenza A Virus in Mice
dc.contributor.authorSeyer, Roman
dc.contributor.authorHrincius, Eike R.
dc.contributor.authorRitzel, Dorothea
dc.contributor.authorAbt, Marion
dc.contributor.authorMellmann, Alexander
dc.contributor.authorMarjuki, Henju
dc.contributor.authorKühn, Joachim
dc.contributor.authorWolff, Thorsten
dc.contributor.authorLudwig, Stephan
dc.contributor.authorEhrhardt, Christina
dc.date.accessioned2018-05-07T16:06:54Z
dc.date.available2018-05-07T16:06:54Z
dc.date.created2012-11-22
dc.date.issued2011-11-18none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/re0SvjKb8EvI/PDF/24f349vf3l84c.pdf
dc.identifier.urihttp://edoc.rki.de/176904/1368
dc.description.abstractInfluenza impressively reflects the paradigm of a viral disease in which continued evolution of the virus is of paramount importance for annual epidemics and occasional pandemics in humans. Because of the continuous threat of novel influenza outbreaks, it is essential to gather further knowledge about viral pathogenicity determinants. Here, we explored the adaptive potential of the influenza A virus subtype H1N1 variant isolate A/Hamburg/04/09 (HH/04) by sequential passaging in mice lungs. Three passages in mice lungs were sufficient to dramatically enhance pathogenicity of HH/04. Sequence analysis identified 4 nonsynonymous mutations in the third passage virus. Using reverse genetics, 3 synergistically acting mutations were defined as pathogenicity determinants, comprising 2 mutations in the hemagglutinin (HA[D222G] and HA[K163E]), whereby the HA(D222G) mutation was shown to determine receptor binding specificity and the polymerase acidic (PA) protein F35L mutation increasing polymerase activity. In conclusion, synergistic action of all 3 mutations results in a mice lethal pandemic H1N1 virus.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut
dc.subjectAmino Acid Sequenceeng
dc.subjectMaleeng
dc.subjectAnimalseng
dc.subjectMiceeng
dc.subjectInfluenza A Viruseng
dc.subjectH1N1 Subtype/geneticseng
dc.subjectNeuraminidase/geneticseng
dc.subjectViral Proteins/geneticseng
dc.subjectPoint Mutationeng
dc.subjectVirulence Factors/geneticseng
dc.subjectMice Inbred BALB Ceng
dc.subjectH1N1 Subtype/pathogenicityeng
dc.subjectHemagglutinins Viral/geneticseng
dc.subjectAmino Acid Substitution/geneticseng
dc.subjectDNA Mutational Analysiseng
dc.subjectInfluenza A Virus H1N1 Subtype/enzymologyeng
dc.subjectModels Animaleng
dc.subjectOrthomyxoviridae Infections/geneticseng
dc.subjectOrthomyxoviridae Infections/physiopathologyeng
dc.subjectProtein Subunits/geneticseng
dc.subjectRNA Replicase/geneticseng
dc.subjectSerial Passageeng
dc.subjectWeight Losseng
dc.subject.ddc610 Medizin
dc.titleSynergistic Adaptive Mutations in the Hemagglutinin and Polymerase Acidic Protein Lead to Increased Virulence of Pandemic 2009 H1N1 Influenza A Virus in Mice
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10028599
dc.identifier.doi10.1093/infdis/jir716
dc.identifier.doihttp://dx.doi.org/10.25646/1293
local.edoc.container-titleJournal of Infectious Diseases
local.edoc.container-textRoman Seyer, Eike R. Hrincius, Dorothea Ritzel, Marion Abt,a, Alexander Mellmann, Henju Marjuki, Joachim Kühn, Thorsten Wolff, Stephan Ludwig, Christina Ehrhardt. Synergistic Adaptive Mutations in the Hemagglutinin and Polymerase Acidic Protein Lead to Increased Virulence of Pandemic 2009 H1N1 Influenza A Virus in Mice. (2012) The Journal of Infectious Diseases, 205 (2), pp. 262-271.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://jid.oxfordjournals.org/content/205/2/262
local.edoc.container-publisher-nameOxford University Press
local.edoc.container-volume205
local.edoc.container-issue2
local.edoc.container-year2012

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