TRANSCELLULAR ACTIVATION OF THE HTLV PROMOTER BY HUMAN HEMATOPOIETIC-CELLS

We examined the ability of hematopoietic cells to transactivate the HT LV promoter by a transcellular mechanism. HeLa cells containing a CAT reporter gene driven by the HTLV-2 promoter were cocultivated with hem atopoietic cells of the B-(Raji), T-(HuT78, Jurkat) and monocyte/promy elocytic (THP-1, U937 and HL60) lineages. Cocultivation with U937 and HuT78 cells constitutively and significantly transactivated the HTLV-2 promoter, while no effect was observed with the other lines. However, activation of other T-cell lines (CEM, Jurkat, Molt-3 and MT-4) with a combination of phorbolester and phytohemagglutinin also resulted in potent transactivation. Supernatant from HuT78 cells exhibited detecta ble transactivating activity, suggesting that the activation is mediat ed by a secreted factor(s). This factor also transactivates the HTLV-1 promoter. We used a panel of HTLV-1 LTR deletion mutants to map the r esponsive elements to this factor(s). Unlike the response element to t he HTLV transactivator protein, Tax, which can be mapped to a small re gion in the enhancer, maximal transactivation by the cellular factor(s ) required the complete U3 sequence. Transcellular activation of the H TLV promoter by activated T-cells may play a role in the development o f leukemia in HTLV infected individuals.