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 language | English (US) |
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Pages (from-to) | 1429-1441 |
Number of pages | 13 |
Journal | EMBO Reports |
Volume | 18 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2017 |
Keywords
- DAI/ZBP1
- IE3
- RIPK3
- murine cytomegalovirus
- necroptosis
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Genetics