TY - JOUR
T1 - Z-form nucleic acid-binding protein 1 (ZBP1) as a sensor of viral and cellular Z-RNAs
T2 - walking the razor's edge
AU - DeAntoneo, Carly
AU - Herbert, Alan
AU - Balachandran, Siddharth
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/8
Y1 - 2023/8
N2 - 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.
AB - 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.
KW - RNA/chemistry
KW - Animals
KW - Humans
KW - Cell Death
KW - Inflammation/metabolism
KW - Mammals/genetics
KW - RNA-Binding Proteins/genetics
KW - Nucleic Acid Conformation
UR - http://www.scopus.com/inward/record.url?scp=85160752317&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:001014826400001&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1016/j.coi.2023.102347
DO - 10.1016/j.coi.2023.102347
M3 - Review article
C2 - 37276820
SN - 0952-7915
VL - 83
SP - 102347
JO - Current Opinion in Immunology
JF - Current Opinion in Immunology
M1 - 102347
ER -