Z-DNA-binding protein-1 (ZBP1), also known as, DNA-dependent activator of IFN-regulatory factors (DAI) was reported to initiate innate immune responses in murine L929 cells upon stimulation by multiple types of exogenously added DNA (Takaoka A et al 2007). Human cytomegalovirus (HCMV) was shown to stimulate ZBP1-mediated induction of IRF3 in human foreskin (DeFilippis VR et al 2010). ZBP1 was also implicated in activation of NF-kappaB pathways in human embryonic kidney HEK293T cells (Kaiser WJ et al 2008, Rebsamen M et al 2009). However, the role and importance ofZBP1 as dsDNA sensor remain controversial, since knocking down ZBP1 expression in other human or murine cell types by siRNA had very little effect on cellular responses to cytosolic DNA, suggesting the presence of alternative pathway (Wang ZC et al 2008, Lippmann J et al 2008). Tissue-specific expression of human ZBP1 also suggests that ZBP1 may function in cell-type specific way (Rothenburg S et al 2002).