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2008-11-19Zeitschriftenartikel DOI: 10.1128/JVI.01558-08
Specific Inhibition of the PKR-Mediated Antiviral Response by the Murine Cytomegalovirus Proteins m142 and m143
dc.contributor.authorBudt, Matthias
dc.contributor.authorNiederstadt, Lars
dc.contributor.authorValchanova, Ralitsa S.
dc.contributor.authorJonjic, Stipan
dc.contributor.authorBrune, Wolfram
dc.date.accessioned2018-05-07T14:18:44Z
dc.date.available2018-05-07T14:18:44Z
dc.date.created2010-12-20
dc.date.issued2008-11-19none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/rehFLndDyBsw/PDF/21hH6ATixeLA.pdf
dc.identifier.urihttp://edoc.rki.de/176904/779
dc.description.abstractDouble-stranded RNA (dsRNA) produced during viral infection activates several cellular antiviral responses. Among the best characterized is the shutoff of protein synthesis mediated by the dsRNA-dependent protein kinase (PKR) and the oligoadenylate synthetase (OAS)/RNase L system. As viral replication depends on protein synthesis, many viruses have evolved mechanisms for counteracting the PKR and OAS/RNase L pathways. The murine cytomegalovirus (MCMV) proteins m142 and m143 have been characterized as dsRNA binding proteins that inhibit PKR activation, phosphorylation of the translation initiation factor eIF2alpha, and a subsequent protein synthesis shutoff. In the present study we analyzed the contribution of the PKR- and the OAS-dependent pathways to the control of MCMV replication in the absence or presence of m142 and m143. We show that the induction of eIF2alpha phosphorylation during infection with an m142- and m143-deficient MCMV is specifically mediated by PKR, not by the related eIF2alpha kinases PERK or GCN2. PKR antagonists of vaccinia virus (E3L) or herpes simplex virus (gamma34.5) rescued the replication defect of an MCMV strain with deletions of both m142 and m143. Moreover, m142 and m143 bound to each other and interacted with PKR. By contrast, an activation of the OAS/RNase L pathway by MCMV was not detected in the presence or absence of m142 and m143, suggesting that these viral proteins have little or no influence on this pathway. Consistently, an m142- and m143-deficient MCMV strain replicated to high titers in fibroblasts lacking PKR but did not replicate in cells lacking RNase L. Hence, the PKR-mediated antiviral response is responsible for the essentiality of m142 and m143.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionskrankheiten / Erreger
dc.subjectAnimalseng
dc.subjectWesterneng
dc.subjectDNAeng
dc.subjectViraleng
dc.subjectMolecular Sequence Dataeng
dc.subjectMiceeng
dc.subjectPhosphorylationeng
dc.subjectRNAeng
dc.subjectDouble-Stranded/metabolismeng
dc.subjecteIF-2 Kinase/metabolismeng
dc.subjectBase Sequenceeng
dc.subjectBlottingeng
dc.subjectCytomegalovirus/metabolismeng
dc.subjectCytomegalovirus/physiologyeng
dc.subjectCytomegalovirus Infections/geneticseng
dc.subjectEukaryotic Initiation Factor-2/metabolismeng
dc.subjectFluorescent Antibody Techniqueeng
dc.subjectImmunoprecipitationeng
dc.subjectNIH 3T3 Cellseng
dc.subjectViral Proteins/physiologyeng
dc.subjecteIF-2 Kinase/antagonists & inhibitorseng
dc.subject.ddc610 Medizin
dc.titleSpecific Inhibition of the PKR-Mediated Antiviral Response by the Murine Cytomegalovirus Proteins m142 and m143
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10011950
dc.identifier.doi10.1128/JVI.01558-08
dc.identifier.doihttp://dx.doi.org/10.25646/704
local.edoc.container-titleJournal of Virology
local.edoc.container-textBudt, M., Niederstadt, L., Valchanova, R.S., Jonjić, S., Brune, W. Specific inhibition of the PKR-mediated antiviral response by the murine cytomegalovirus proteins m142 and m143 (2009) Journal of Virology, 83 (3), pp. 1260-1270.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://jvi.asm.org/cgi/content/short/83/3/1260
local.edoc.container-publisher-nameAmerican Society for Microbiology
local.edoc.container-volume83
local.edoc.container-issue3
local.edoc.container-year2009

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