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 Kaiser, Jason W. Upton

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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
Volume18
Issue number8
DOIs
StatePublished - Aug 1 2017

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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    Sridharan, H., Ragan, K. B., Guo, H., Gilley, R. P., Landsteiner, V. J., Kaiser, W., & Upton, J. W. (2017). Murine cytomegalovirus IE3-dependent transcription is required for DAI/ZBP1-mediated necroptosis. EMBO Reports, 18(8), 1429-1441. https://doi.org/10.15252/embr.201743947