ACTIVATION OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-1 TAX GENE-EXPRESSION IN CHRONICALLY INFECTED T-CELLS

Expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated both by the HTLV-1 Tax transactivator and by cellular transcriptional factors binding to the viral long terminal repeat (LTR), suggesting t hat cellular signals may play a role in regulating viral expression. T reatment of cells chronically infected with HTLV-1, which express low levels of HTLV-1 RNAs and Tax protein, with phorbol esters (i.e., phor bol12-myristate 13-acetate [PMA]), phytohemagglutinin (PHA), sodium bu tyrate, or combinations of cytokines resulted in induction of HTLV-1 g ene expression. PMA or PHA treatment following cotransfection of HTLV- 1 Tax expression plasmids resulted in synergistic activation of HTLV-1 LTR directed gene expression, apparently involving tyrosine ki nase-m ediated pathways. These results suggest that cellular activation stimu li may cooperate with HTLV-1 Tax to enhance expression of integrated H TLV-1 genomes and thus may play a role in the pathogenesis of HTLV-1 d isease.