TRANSCRIPTIONAL ACTIVATION OF THE INTERLEUKIN-6 GENE BY HTLV-1 P40TAX THROUGH AN NF-KAPPA-B-LIKE BINDING-SITE

The interleukin-6 (IL-6) gene is expressed by various stimuli including cytokines or viral infections, such as human T-cell leukemia virus type I (HTLV-1). However, it has not been well established how HTLV-1 induces the expression of the IL-6 gene. In the present study, we demonstrated that HTLV-1-derived transactivator protein, p40tax, could stimulate endogenous IL-6 gene expression. Furthermore, we showed that the NF-kappaB binding site (IL-6kappaB site) located between -74 and -62 upstream of the cap site of the IL-6 gene was an essential cis-acting element for p40tax-mediated transactivation of the IL-6 gene expression by utilizing a series of 5' deletion mutants of the IL-6 5' flanking region as well as a construct with a mutated IL-6kappaB site. We identified the presence of two nuclear factor complexes that bound to the IL-6kappaB site. One was constitutively expressed, and the other was inducible by p40tax. Taken together, HTLV-1 p40tax directly induces IL-6 gene expression through the IL-6kappaB site, indicating the close association between IL-6 overproduction and HTLV-1 infection.