Pregled bibliografske jedinice broj: 1107363
The Cytomegalovirus Tegument Protein UL35 Antagonizes Pattern Recognition Receptor- Mediated Type I IFN Transcription
The Cytomegalovirus Tegument Protein UL35 Antagonizes Pattern Recognition Receptor- Mediated Type I IFN Transcription // Microorganisms, 8 (2020), 6; 790, 26 doi:10.3390/microorganisms8060790 (međunarodna recenzija, članak, znanstveni)
CROSBI ID: 1107363 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
The Cytomegalovirus Tegument Protein UL35
Antagonizes Pattern Recognition Receptor-
Mediated Type I IFN Transcription
Autori
Fabits, Markus ; Gonçalves Magalhães, Vladimir ; Chan, Baca ; Girault, Virginie ; Elbasani, Endrit ; Rossetti, Elisa ; Saeland, Eirikur ; Messerle, Martin ; Pichlmair, Andreas ; Lisnić, Vanda Juranić ; Brinkmann, Melanie M.
Izvornik
Microorganisms (2076-2607) 8
(2020), 6;
790, 26
Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni
Ključne riječi
herpesvirus ; cytomegalovirus ; pattern recognition receptor ; cGAS ; STING ; RIG-I ; TBK1 ; UL35 ; type I interferon ; OGT
Sažetak
Abstract: The 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.
Izvorni jezik
Engleski
Znanstvena područja
Temeljne medicinske znanosti
Citiraj ovu publikaciju:
Časopis indeksira:
- Web of Science Core Collection (WoSCC)
- Science Citation Index Expanded (SCI-EXP)
- SCI-EXP, SSCI i/ili A&HCI
- Scopus
