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

摘要

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 style="fixed-case">DAI/ style="fixed-case">ZBP1 during natural viral infection.