Human T cell lymphotropic virus type I tax activates IL-15Rα gene expression through an NF-κB site

IL-15 mRNA levels are increased in diseases caused by human T cell lymphotropic virus type I(HTLV-I), In this study, we demonstrated that IL-15R alpha, the IL-15-specific binding receptor, mRNA and protein levels were also elevated in HTLV-I-infected cells, We showed that transient HTLV-I Tax expression lead to increased IL-15R alpha mRNA levers. In addition, by using a reporter construct that bears the human IL-15R alpha promoter, we demonstrated that Tax expression increased promoter activity by at least 4-fold. Furthermore, using promoter deletion constructs and gel shift analysis, we defined a functional NF-kappaB-binding motif in the human IL-15R alpha promoter, suggesting that Tax activation of IL-15R alpha is due, in part, to the induction of NF-kappaB. These data indicate that IL-15R alpha is transcriptionally regulated by the HTLV-I Tax protein through the action of NF-kappaB. These findings suggest a role far IL-15R alpha in aberrant T cell proliferation observed in HTLV-I-associated diseases. The Journal of Immunology, 2001, 166: 2602-2609.