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.

Z 型核酸结合蛋白 1 (ZBP1) 可检测病毒 Z 型 RNA (Z-RNA)，激活受体相互作用蛋白激酶 3，并在 RNA 和 DNA 病毒感染期间触发细胞死亡。这种细胞死亡通过消除受感染的细胞和激发抗病毒免疫来促进病毒清除，因此常常成为病毒编码抑制因子逃避的目标。最近的证据表明，ZBP1 也可以被哺乳动物基因组内源性逆转录因子转录的细胞 Z-RNA 激活。这些细胞 Z-RNA 如果不被腺苷脱氨酶 RNA 特异性 1 编辑和中和，则会引发 ZBP1 依赖性细胞死亡和炎症，从而可能导致 Aicardi-Goutière 综合征和相关干扰素病。因此，虽然在感染过程中病毒 Z-RNA 对 ZBP1 的良好控制激活是有益的，但在其他疾病环境中，当细胞 Z-RNA 不当触发时，相同的途径可能会产生有害后果。