Biological function of the vaccinia virus Z-DNA-binding protein E3L: Gene transactivation and antiapoptotic activity in HeLa cells

The vaccinia virus (VV) E3L protein is essential for virulence and has anti-apoptotic activity. In mice, Z-DNA-binding activity of the N-terminal domain of E3L (Z alpha) is necessary for viral lethality. Here, we report that inhibition of hygromycin-B-induced apoptosis in HeLa cells depends on Z-DNA binding of the E3L Z alpha domain. Z-DNA-binding domains of other proteins are equally effective in blocking apoptosis. Using a transient reporter assay, we demonstrate transactivation of human IL-6, nuclear factor of activated T cells (NF-AT), and p53 genes by E3L. This activation also requires Z-DNA binding of the N-terminal domain of E3L. Overall, this work suggests that the important role of E3L in VV pathogenesis involves modulating expression of host cellular genes at the transcriptional level and inhibiting apoptosis of host cells through Z-DNA binding.