TATA-DEPENDENT REPRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TRANSCRIPTION BY THE ADENOVIRUS E1A 243R ONCOPROTEIN

Human adenovirus E1A oncoprotein activates or represses transcription from a variety of viral and cellular promoters by several complex mech anisms. The E1A products, 289R and 243R, have differential effects on transcription directed by the human immunodeficiency virus type 1 (HIV -1) long terminal repeat (LTR). Previous reports indicate that repress ion of HIV-1 LTR-directed gene expression by E1A 243R is mediated thro ugh the kappa B enhancer elements located between nucleotides -105 and -82 relative to the transcription initiation start site (+1). Results from this study suggest a novel mechanism for transcriptional repress ion of the HIV-1 LTR by E1A 243R that is enhancer-independent and that is mediated through basal HIV-1 promoter elements. Transient expressi on assays, in which 5'-truncated or site-directed mutant HIV-1 LTR-CAT reporters were tested for their response to repression mediated by wi ld-type or mutant 243R, demonstrate that LTR sequences upstream of -31 relative to the transcription initiation start site (+1) and inclusiv e of the enhancer elements are dispensable for 243R-mediated repressio n. The ability of 243R to repress HIV-1 basal promoter activity requir es both an intact N-terminus of E1A 243R and the TATA element within t he HIV-1 promoter. These results support a novel mechanism for E1A 243 R-induced transcriptional repression that is enhancer-independent and that targets directly the general transcription machinery.