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Publication : Murine cytomegalovirus IE3-dependent transcription is required for DAI/ZBP1-mediated necroptosis.

First Author  Sridharan H Year  2017
Journal  EMBO Rep Volume  18
Issue  8 Pages  1429-1441
PubMed ID  28607035 Mgi Jnum  J:289444
Mgi Id  MGI:5927398 Doi  10.15252/embr.201743947
Citation  Sridharan H, et al. (2017) Murine cytomegalovirus IE3-dependent transcription is required for DAI/ZBP1-mediated necroptosis. EMBO Rep 18(8):1429-1441
abstractText  DNA-dependent activator of interferon regulatory factors/Z-DNA binding protein 1 (DAI/ZBP1) is a crucial sensor of necroptotic cell death induced by murine cytomegalovirus (MCMV) in its natural host. Here, we show that viral capsid transport to the nucleus and subsequent viral IE3-dependent early transcription are required for necroptosis. Necroptosis induction does not depend on input virion DNA or newly synthesized viral DNA A putative RNA-binding domain of DAI/ZBP1, Zalpha2, is required to sense virus and trigger necroptosis. Thus, MCMV IE3-dependent transcription from the viral genome plays a crucial role in activating DAI/ZBP1-dependent necroptosis. This implicates RNA transcripts generated by a large double-stranded DNA virus as a biologically relevant ligand for DAI/ZBP1 during natural viral infection.
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