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2013-08-08Zeitschriftenartikel DOI: 10.1371/journal.ppat.1003544
Cytomegalovirus Downregulates IRE1 to Repress the Unfolded Protein Response
dc.contributor.authorStahl, Sebastian
dc.contributor.authorBurkhart, Julia M.
dc.contributor.authorHinte, Florian
dc.contributor.authorTirosh, Boaz
dc.contributor.authorMohr, Hermine
dc.contributor.authorZahedi, René P.
dc.contributor.authorSickmann, Albert
dc.contributor.authorRuzsics, Zsolt
dc.contributor.authorBudt, Matthias
dc.contributor.authorBrune, Wolfram
dc.date.accessioned2018-05-07T17:00:53Z
dc.date.available2018-05-07T17:00:53Z
dc.date.created2013-09-13
dc.date.issued2013-08-08none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/reHM5oIYfWD0Y/PDF/226PDID9SO216.pdf
dc.identifier.urihttp://edoc.rki.de/176904/1662
dc.description.abstractDuring viral infection, a massive demand for viral glycoproteins can overwhelm the capacity of the protein folding and quality control machinery, leading to an accumulation of unfolded proteins in the endoplasmic reticulum (ER). To restore ER homeostasis, cells initiate the unfolded protein response (UPR) by activating three ER-to-nucleus signaling pathways, of which the inositol-requiring enzyme 1 (IRE1)-dependent pathway is the most conserved. To reduce ER stress, the UPR decreases protein synthesis, increases degradation of unfolded proteins, and upregulates chaperone expression to enhance protein folding. Cytomegaloviruses, as other viral pathogens, modulate the UPR to their own advantage. However, the molecular mechanisms and the viral proteins responsible for UPR modulation remained to be identified. In this study, we investigated the modulation of IRE1 signaling by murine cytomegalovirus (MCMV) and found that IRE1-mediated mRNA splicing and expression of the X-box binding protein 1 (XBP1) is repressed in infected cells. By affinity purification, we identified the viral M50 protein as an IRE1-interacting protein. M50 expression in transfected or MCMV-infected cells induced a substantial downregulation of IRE1 protein levels. The N-terminal conserved region of M50 was found to be required for interaction with and downregulation of IRE1. Moreover, UL50, the human cytomegalovirus (HCMV) homolog of M50, affected IRE1 in the same way. Thus we concluded that IRE1 downregulation represents a previously undescribed viral strategy to curb the UPR.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut
dc.subjectAnimalseng
dc.subjectHumanseng
dc.subjectMiceeng
dc.subjectDNA-Binding Proteins/geneticseng
dc.subjectDNA-Binding Proteins/metabolismeng
dc.subjectMembrane Proteins/geneticseng
dc.subjectTranscription Factors/geneticseng
dc.subjectTranscription Factors/metabolismeng
dc.subjectCytomegalovirus/geneticseng
dc.subjectCell Line Transformedeng
dc.subjectCytomegalovirus/metabolismeng
dc.subjectCytomegalovirus Infections/geneticseng
dc.subjectCytomegalovirus Infections/metabolismeng
dc.subjectDown-Regulation/geneticseng
dc.subjectEndoribonucleases/biosynthesiseng
dc.subjectEndoribonucleases/geneticseng
dc.subjectMembrane Proteins/biosynthesiseng
dc.subjectMuromegalovirus/geneticseng
dc.subjectMuromegalovirus/metabolismeng
dc.subjectNIH 3T3 Cellseng
dc.subjectProtein-Serine-Threonine Kinases/biosynthesiseng
dc.subjectProtein-Serine-Threonine Kinases/geneticseng
dc.subjectUnfolded Protein Responseeng
dc.subjectViral Structural Proteins/geneticseng
dc.subjectViral Structural Proteins/metabolismeng
dc.subject.ddc610 Medizin
dc.titleCytomegalovirus Downregulates IRE1 to Repress the Unfolded Protein Response
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10032760
dc.identifier.doi10.1371/journal.ppat.1003544
dc.identifier.doihttp://dx.doi.org/10.25646/1587
local.edoc.container-titlePLoS Pathogens
local.edoc.container-textStahl S, Burkhart JM, Hinte F, Tirosh B, Mohr H, et al. (2013) Cytomegalovirus Downregulates IRE1 to Repress the Unfolded Protein Response. PLoS Pathog 9(8): e1003544.
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.1003544
local.edoc.container-publisher-namePublic Library of Science
local.edoc.container-volume9
local.edoc.container-issue8
local.edoc.container-year2013

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