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2009-06-12Zeitschriftenartikel DOI: 10.1371/journal.ppat.1000473
Influenza B virus ribonucleoprotein is a potent activator of the antiviral kinase PKR
dc.contributor.authorDauber, Bianca
dc.contributor.authorMartinez-Sobrido, Luis
dc.contributor.authorSchneider, Jana
dc.contributor.authorHai, Rong
dc.contributor.authorWaibler, Zoe
dc.contributor.authorKalinke, Ulrich
dc.contributor.authorGarcis-Sastre, Adolfo
dc.contributor.authorWolff, Thorsten
dc.date.accessioned2018-05-07T13:16:23Z
dc.date.available2018-05-07T13:16:23Z
dc.date.created2009-07-02
dc.date.issued2009-06-12none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/remewyVRS0Wk/PDF/240FKQvRXBTng.pdf
dc.identifier.urihttp://edoc.rki.de/176904/443
dc.description.abstractActivation of the latent kinase PKR is a potent innate defense reaction of vertebrate cells towards viral infections, which is triggered by recognition of viral double-stranded (ds) RNA and results in a translational shutdown. A major gap in our understanding of PKR's antiviral properties concerns the nature of the kinase activating molecules expressed by influenza and other viruses with a negative strand RNA genome, as these pathogens produce little or no detectable amounts of dsRNA. Here we systematically investigated PKR activation by influenza B virus and its impact on viral pathogenicity. Biochemical analysis revealed that PKR is activated by viral ribonucleoprotein (vRNP) complexes known to contain single-stranded RNA with a 5'-triphosphate group. Cell biological examination of recombinant viruses showed that the nucleo-cytoplasmic transport of vRNP late in infection is a strong trigger for PKR activation. In addition, our analysis provides a mechanistic explanation for the previously observed suppression of PKR activation by the influenza B virus NS1 protein, which we show here to rely on complex formation between PKR and NS1's dsRNA binding domain. The high significance of this interaction for pathogenicity was revealed by the finding that attenuated influenza viruses expressing dsRNA binding-deficient NS1 proteins were rescued for high replication and virulence in PKR-deficient cells and mice, respectively. Collectively, our study provides new insights into an important antiviral defense mechanism of vertebrates and leads us to suggest a new model of PKR activation by cytosolic vRNP complexes, a model that may also be applicable to other negative strand RNA viruses.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionskrankheiten / Erreger
dc.subjectCell Lineeng
dc.subjectTumoreng
dc.subjectHumanseng
dc.subjectFemaleeng
dc.subjectActive Transporteng
dc.subjectCell Nucleueng
dc.subjectAnimalseng
dc.subjectCellseng
dc.subjectCulturedeng
dc.subjectCytoplasm/metabolismeng
dc.subjectEnzyme Activationeng
dc.subjectInfluenza B virus/geneticseng
dc.subjectInfluenza B virus/pathogenicityeng
dc.subjectInfluenza B virus/physiologyeng
dc.subjectMiceeng
dc.subjectInbred C57BLeng
dc.subjectMicroscopyeng
dc.subjectFluorescenceng
dc.subjectModelseng
dc.subjectBiologicaleng
dc.subjectPhosphorylationeng
dc.subjectRNAeng
dc.subjectDouble-Stranded/metabolismeng
dc.subjectRNA-Binding Proteins/geneticseng
dc.subjectRNA-Binding Proteins/metabolismeng
dc.subjectRibonucleoproteins/metabolismeng
dc.subjectViral Nonstructural Proteins/geneticseng
dc.subjectViral Nonstructural Proteins/metabolismeng
dc.subjectViral Proteins/metabolismeng
dc.subjectVirus Replicationeng
dc.subjecteIF-2 Kinase/metabolismeng
dc.subject.ddc610 Medizin
dc.titleInfluenza B virus ribonucleoprotein is a potent activator of the antiviral kinase PKR
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-1001227
dc.identifier.doi10.1371/journal.ppat.1000473
dc.identifier.doihttp://dx.doi.org/10.25646/368
local.edoc.container-titlePLoS Pathogens
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000473
local.edoc.container-publisher-namePublic Library of Science
local.edoc.container-volume5
local.edoc.container-issue6
local.edoc.container-year2009

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