Z-DNA-binding protein 1 (also known as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1) is an intracellular protein in mammals that can activate an innate immune pathways to suppress the viral infection. ZENB1 senses left-handed (Z-form) double-helical Z-DNA and Z-RNA, which are pathogen-associated molecular patterns (PAMPs). It associates with Receptor Interacting Protein Kinase 3 (RIPK3) to initiate PANoptosis, a form of inflammatory programmed cell death.
During infection of human cells with influenza A virus (IAV) and HSV-1, host cell-derived Z-RNAs, arising from viral disruption of host transcription termination, are detected by ZBP1 to initiate NF-κB signalling and PANoptosis.
ZBP1 is an abbreviation for chicken or rat β-actin zipcode-binding protein 1. In humans, it is encoded by the ZBP1 gene. It is a homolog of the human insulin-like growth factor 2 mRNA-binding protein 1 (IMP-1) and murine CRD-BP, the proteins involved in mRNA transport (RNA-binding proteins, RBPs).