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

Haripriya Sridharan, Katherine B. Ragan, Hongyan Guo, Ryan P. Gilley, Vanessa J. Landsteiner, William J. Kaiser, Jason W. Upton

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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, Zα2, 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.

Original languageEnglish (US)
Pages (from-to)1429-1441
Number of pages13
JournalEMBO Reports
Issue number8
StatePublished - Aug 2017


  • DAI/ZBP1
  • IE3
  • RIPK3
  • murine cytomegalovirus
  • necroptosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics


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