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Murine cytomegalovirus IE 3‐dependent transcription is required for DAI / ZBP 1‐mediated necroptosis
Author(s) -
Sridharan Haripriya,
Ragan Katherine B,
Guo Hongyan,
Gilley Ryan P,
Landsteiner Vanessa J,
Kaiser William J,
Upton Jason W
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201743947
Subject(s) - necroptosis , transcription (linguistics) , biology , virology , interferon , microbiology and biotechnology , rna , virus , dna , programmed cell death , gene , genetics , apoptosis , linguistics , philosophy
DNA ‐dependent activator of interferon regulatory factors/Z‐ DNA binding protein 1 ( DAI / ZBP 1) 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 IE 3‐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 / ZBP 1, Zα2, is required to sense virus and trigger necroptosis. Thus, MCMV IE 3‐dependent transcription from the viral genome plays a crucial role in activating DAI / ZBP 1‐dependent necroptosis. This implicates RNA transcripts generated by a large double‐stranded DNA virus as a biologically relevant ligand for DAI / ZBP 1 during natural viral infection.