Characterization of the promoter region of the viral interferon regulatory factor encoded by Kaposi's sarcoma-associated herpesvirus.

Viral interferon regulatory factor (vIRF) encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) inhibits the expression of interferon-responsive genes, causes cellular transformation and transactivates KSHV genes. In the present study, we characterized the mRNA expression pattern of the vIRF gene and its promoter. A vIRF transcript of 1.7 kb in size was detected in low level in uninduced KSHV-infected cells and its expression was inducible by 12-O-tetradecanoylphorbol-13-acetate (TPA), sensitive to cycloheximide and resistant to phosphonoacetic acid. The transcription start site was mapped to 79 nt upstream of the ATG initiation site by 5'-RACE. Mutagenesis analysis identified a region between -56 and the transcription start site (+1) as the minimal promoter region that contains a functional TATA box at -27. A region between -337 and -125 contains a repressor domain negated by sequence from -991 to -499 in BCBL-1 cells, a region which was also identified to be responsive to TPA induction. These results demonstrate vIRF as a KSHV early gene, identify its promoter and define the promoter regions that contain regulatory elements controlling vIRF transcription.