New hybrid or chimeric fusion polypeptide transcription regulators which induce interferon target gene expression are provided for use in anti-viral and anti-proliferative applications. The hybrid fusion proteins comprise the p48 interferon regulatory factor protein, or a functional portion thereof, fused to a transcriptional activation domain (TAD), or a functional portion thereof. More specifically, the p48 interferon regulatory factor protein is fused to a STAT transcriptional activation do main (TAD) (p48-STAT TAD). A particular p48-STAT TAD is p48-S2C, in which S2C is the TAD of STAT2. Another p48-TAD is p48-VP16 TAD, in which p48 is fused to the transcriptional activation domain of the VP16 protein of Herpes Simplex Virus (HSV). The p48-TAD nucleic acid sequences and encoded polypeptides can be employed for anti-viral treatment and for the treatment of cancers, tumors and neoplastic diseases.