TRANSCRIPTION FACTOR PRDII-BF1 ACTIVATES HUMAN-IMMUNODEFICIENCY-VIRUSTYPE-1 GENE-EXPRESSION

Gene expression of human immunodeficiency virus (HIV) is modulated by both cellular transcription factors, which bind to cis-acting regulato ry elements in the HIV-1 long terminal repeat (LTR) and the viral tran sactivator, tat. The enhancer element in the HIV-1 LTR which extends f rom -103 to -82 is critical for gene expression. This region contains two identical IO-bp direct repeats which serve as binding sites for me mbers of the NF-kappa B family of transcription factors. However, seve ral other cellular transcription factors, including a group of zinc fi nger DNA-binding proteins, also bind to NF-kappa B and related motifs. A member of this family of transcription factors, designated PRDII-BF 1 or MBP-1, is a 300-kDa cellular protein which contains two widely se parated zinc finger DNA binding domains. Each of these binding domains is capable of binding to NF-kappa B or related recognition moths. Sin ce no functional role for this protein has been demonstrated in the re gulation of viral and cellular promoters, we began studies to determin e whether PRDII-BF1 could modulate HIV-1 gene expression. DNase I foot printing of the HIV-1 LTR indicated that PRDII-BP1 bound to both NF-KB and TAR transactivation response DNA elements. Both in vitro translat ion and vaccinia virus expression of PRDII-BF1 cDNA resulted in the sy nthesis of the full-length 300-kDa PRDII-BF1 protein. Transfection exp eriments, using both eucaryotic expression vectors and antisense const ructs, indicated that PRDII-BF1 activated HIV-I gene expression in bot h the presence and absence of tal, These results are consistent with a role for PRDII-BP1 in activating HIV-1 gene expression.