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 that cellular signals may play a role in regulating viral expression. Treatment of cells chronically infected with HTLV-1, which express low levels of HTLV-1 RNAs and Tax protein, with phorbol esters (i.e., phorbol12-myristate 13- acetate [PMA]), phytohemagglutinin (PHA), sodium butyrate, or combinations of cytokines resulted in induction of HTLV- 1 gene 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- mediated pathways. These results suggest that cellular activation stimuli may cooperate with HTLV-1 Tax to enhance expression of integrated HTLV-1 genomes and thus may play a role in the pathogenesis of HTLV-1 disease.