Transcellular activation of the HTLV promoter by human hematopoietic cells.
We examined the ability of hematopoietic cells to transactivate the HTLV promoter by a transcellular mechanism. HeLa cells containing a CAT reporter gene driven by the HTLV-2 promoter were cocultivated with hematopoietic cells of the B-(Raji), T-(HuT78, Jurkat) and monocyte/promyelocytic (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 detectable transactivating activity, suggesting that the activation is mediated 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 responsive elements to this factor(s). Unlike the response element to the HTLV transactivator protein, Tax, which can be mapped to a small region in the enhancer, maximal transactivation by the cellular factor(s) required the complete U3 sequence. Transcellular activation of the HTLV promoter by activated T-cells may play a role in the development of leukemia in HTLV infected individuals.
Baier-Bitterlich
G
G
La Jolla Institute for Allergy and Immunology, California.
Rappaport
J
J
Baier
G
G
Looney
D
D
Wong-Staal
F
F
D017977:Deltaretrovirus / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008213:Lymphocyte Activation; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000502:physiology*; D015533:Transcriptional Activation