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dc.contributor.authorFabits, Markus
dc.contributor.authorGonçalves Magalhães, Vladimir
dc.contributor.authorChan, Baca
dc.contributor.authorGirault, Virginie
dc.contributor.authorElbasani, Endrit
dc.contributor.authorRossetti, Elisa
dc.contributor.authorSaeland, Eirikur
dc.contributor.authorMesserle, Martin
dc.contributor.authorPichlmair, Andreas
dc.contributor.authorLisnić, Vanda Juranić
dc.contributor.authorBrinkmann, Melanie M
dc.date.accessioned2021-01-27T14:34:40Z
dc.date.available2021-01-27T14:34:40Z
dc.date.issued2020-05-26
dc.identifier.citationMicroorganisms. 2020 May 26;8(6):790. doi: 10.3390/microorganisms8060790.en_US
dc.identifier.issn2076-2607
dc.identifier.pmid32466380
dc.identifier.doi10.3390/microorganisms8060790
dc.identifier.urihttp://hdl.handle.net/10033/622706
dc.description.abstractThe rapid activation of pattern recognition receptor (PRR)-mediated type I interferon (IFN) signaling is crucial for the host response to infection. In turn, human cytomegalovirus (HCMV) must evade this potent response to establish life-long infection. Here, we reveal that the HCMV tegument protein UL35 antagonizes the activation of type I IFN transcription downstream of the DNA and RNA sensors cGAS and RIG-I, respectively. We show that ectopic expression of UL35 diminishes the type I IFN response, while infection with a recombinant HCMV lacking UL35 induces an elevated type I IFN response compared to wildtype HCMV. With a series of luciferase reporter assays and the analysis of signaling kinetics upon HCMV infection, we observed that UL35 downmodulates PRR signaling at the level of the key signaling factor TANK-binding kinase 1 (TBK1). Finally, we demonstrate that UL35 and TBK1 co-immunoprecipitate when co-expressed in HEK293T cells. In addition, we show that a previously reported cellular binding partner of UL35, O-GlcNAc transferase (OGT), post-translationally GlcNAcylates UL35, but that this modification is not required for the antagonizing effect of UL35 on PRR signaling. In summary, we have identified UL35 as the first HCMV protein to antagonize the type I IFN response at the level of TBK1, thereby enriching our understanding of how this important herpesvirus escapes host immune responses.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectherpesvirus, cytomegalovirus, pattern recognition receptor, cGAS, STING, RIG-I, TBK1, UL35, type I interferon, OGTen_US
dc.subjectherpesvirusen_US
dc.subjectcytomegalovirusen_US
dc.subjectpattern recognition receptoren_US
dc.subjectcGASen_US
dc.subjectSTINGen_US
dc.subjectRIG-Ien_US
dc.subjectTBK1en_US
dc.titleThe Cytomegalovirus Tegument Protein UL35 Antagonizes Pattern Recognition Receptor-Mediated Type I IFN Transcription.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalMicroorganismsen_US
dc.source.volume8
dc.source.issue6
refterms.dateFOA2021-01-27T14:34:41Z
dc.source.journaltitleMicroorganisms
dc.source.countrySwitzerland


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