Bach2, a bZIP transcription factor originally identified as interacting with the small Maf family of bZIP proteins, has been shown to play important roles in oxidative stress-mediated cell death. Here, we examine the role of Bach2 in cell death during double-stranded (ds)RNA-and dsDNA-triggered antiviral innate immune responses. Bach2 expression was induced in HeLa cells upon dsRNA/dsDNA treatment and the suppression of Bach2 expression by siRNA treatment alleviated cell death triggered by dsRNA and dsDNA. Unexpectedly, DNA microarray analysis revealed that siRNA-mediated suppression of Bach2 resulted in the attenuated activation of genes involved in the antiviral innate immune response after dsRNA treatment. Our study thus demonstrates a novel role for Bach2 as a key regulator of nucleic acid-triggered antiviral responses in human cells. (c) 2007 Elsevier Inc. All rights reserved.