HTLV-I tax gene product activates transcription via pre-existing cellular factors and cAMP responsive element.

Human T-cell leukemia virus type I (HTLV-I) is the etiological agent of adult T-cell leukemia. The 3' end of HTLV-I proviral DNA encodes the synthesis of two regulatory proteins, tax and rex. The 40-kDa tax protein is a nuclear protein which positively stimulates transcription from the U3 region of the viral long terminal repeat sequence. Three 21-base pair sequences in the U3 region have been found to serve as the cis-element for tax-mediated trans-activation. We now report that the tax protein can trans-activate HTLV-I LTR in the absence of de novo cellular protein synthesis. Saturated mutagenesis of the 21-base pair repeat sequence showed that specific mutations clustered in sequences homologous to the cAMP responsive element (TGACGTCA) abolish trans-activation by tax. Furthermore, although the TGACGTCN element is nearly palindromic, the mutations that abolish trans-activation are localized exclusively in the 5' 6 bases, suggesting the orientation of this element may play a role in transcription. That the purified tax protein does not bind the 21-base pair repeats or nonspecific DNA lends further support to the notion that tax protein does not directly interact with the 21-base pair repeats to activate transcription. Instead, tax most likely acts via cellular transcriptional factor(s) to bring about trans-activation.