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

作者：Sridharan Haripriya; Ragan Katherine B; Guo Hongyan; Gilley Ryan P; Landsteiner Vanessa J; Kaiser William J; Upton Jason W^*

来源：EMBO Reports, 2017, 18(8): 1429-1441.

DOI：10.15252/embr.201743947

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

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, Z alpha 2, 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.

• 出版日期2017-8