THE CELLULAR STRESS-RESPONSE ENHANCES HUMAN T-CELL LYMPHOTROPIC VIRUSTYPE-1 BASAL GENE-EXPRESSION THROUGH THE CORE PROMOTER REGION OF THE LONG TERMINAL REPEAT

Viral protein expression is postulated to play a critical role in the pathogenesis of human T-cell lymphotropic virus type 1 (HTLV-1)-associ ated diseases. Therefore, knowledge of the cellular events which initi ate or enhance viral gene expression is important in understanding the mechanism of HTLV-1-induced disease. In this report, we examined the modulation of transcription of the HTLV-1 long terminal repeat (LTR) f ollowing induction of the cellular stress response, We demonstrate by both in vitro transcription assays and transient transfections that in duction of the stress response increases basal transcription from the LTR. Transient cotransfection assays indicate that stress induction of viral transcription is Tax independent, In addition, we provide evide nce that the sequences responsible for the enhanced transcription are -52 through +157 of the U3/R region of the HTLV-I LTR. Finally, our da ta suggest that the increase in transcription is mediated through an i ntermediate polymerase II/polymerase III transcriptional complex, demo nstrated by the inability to abolish the effect with low concentration s of alpha-amanitin.