ZBP1: Innate Sensor Regulating Cell Death and Inflammation

Trends Immunol. 2018 Feb;39(2):123-134. doi: 10.1016/j.it.2017.11.002. Epub 2017 Nov 25.


Z-DNA-binding protein 1 (ZBP1), initially reported as an interferon (IFN)-inducible tumor-associated protein, harbors nucleic acid-binding domains for left-handed helix (Z-form) and receptor-interacting protein homotypic interaction motif (RHIM) domains for protein homotypic interactions. Recent studies have identified ZBP1 as an innate sensor of viral infections and a target of viral evasion strategies, regulating cell death, inflammasome activation, and proinflammatory responses. ZBP1 also functions during development and can trigger perinatal lethality when its RHIM-dependent interactions are not restricted. Here we review the history and emergence of ZBP1 as a pathogen sensor and a central regulator of cell death and inflammatory responses. We also discuss the gaps in our knowledge regarding the regulation and functions of ZBP1 and highlight potential avenues for future research.

Keywords: DAI; RIPK1; RIPK3; ZBP1; caspase-8; cell death; inflammasome; inflammation; innate immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Death / immunology*
  • DNA, Z-Form / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Immune Evasion
  • Immunity, Innate
  • Immunomodulation
  • Inflammation / immunology*
  • Protein Domains / genetics
  • RNA-Binding Proteins
  • Signal Transduction
  • Virus Diseases / immunology*


  • DNA, Z-Form
  • DNA-Binding Proteins
  • RNA-Binding Proteins
  • ZBP1 protein, human