CONSTITUTIVE EXPRESSION OF THE HTLV-I PX AND ENV REGIONS IN JURKAT T-CELLS INDUCES DIFFERENTIAL ACTIVATION OF SRE, CRE AND NF-KAPPA-B PATHWAYS

Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukem ia/lymphoma (ATLL). HTLV Tax, the viral transcriptional activator, can activate a variety of cellular genes. HTLV-mediated T-cell transforma tion, however, may involve additional viral proteins expressed from si ngly-as well as doubly-spliced viral mRNA. To determine the combined e ffect of these viral proteins on cellular gene expression in Jurkat T- cells, we derived stable transfectants that constitutively express the HTLV-I pX and env regions (J3.9), J3.9 cells show substantially incre ased mRNA levels of egr-1 and c-jun but no induction of either CD25 or GM-CSF by Northern blotting. This pattern corresponded to the activat ion of an egr-1 but not a GM-CSF promoter-driven reporter construct in transient gene expression assays. In DNA electrophoretic mobility shi ft assays (EMSA), nuclear extract from J3.9 cells has significantly in creased binding to CRE and SRE but not nuclear factor kappa B (NF kapp a B) DNA oligos, as compared to J-Neo cell extract. These results sugg est that low level expression of pX and env region gene products in Ju rkat T-cells stimulates persistent activation of CRE- and SRE- but not NF kappa B-induced cellular genes.