Z-form nucleic acid-binding protein 1 (ZBP1) as a sensor of viral and cellular Z-RNAs: walking the razor's edge

Carly DeAntoneo, Alan Herbert, Siddharth Balachandran

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

Abstract

Z-form nucleic acid-binding protein 1 (ZBP1) detects viral Z-form RNAs (Z-RNAs), activates receptor-interacting protein kinase 3, and triggers cell death during both RNA and DNA virus infections. Such cell death promotes virus clearance by eliminating infected cells and galvanizing antiviral immunity, and is thus often targeted for evasion by virus-encoded suppressors. Recent evidence demonstrates that ZBP1 can also be activated by cellular Z-RNAs transcribed from endogenous retroelements within mammalian genomes. These cellular Z-RNAs, if not edited and neutralized by adenosine deaminase RNA-specific 1, trigger ZBP1-dependent cell death and inflammation, which may drive disease in Aicardi–Goutière's syndrome and related interferonopathies. Thus, while well-controlled activation of ZBP1 by viral Z-RNAs during infections is beneficial, the same pathway can have harmful consequences when inappropriately triggered by cellular Z-RNAs in other disease settings.

Original languageEnglish
Article number102347
Pages (from-to)102347
JournalCurrent Opinion in Immunology
Volume83
DOIs
StatePublished - Aug 2023

Keywords

  • RNA/chemistry
  • Animals
  • Humans
  • Cell Death
  • Inflammation/metabolism
  • Mammals/genetics
  • RNA-Binding Proteins/genetics
  • Nucleic Acid Conformation

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