Both the interleukin-2 receptor-alpha (Tat,~ 55, IL-2Ra) gene and the long terminal repeat (LTR) of type 1 HIV are activated by various T cell mitogens. We now demonstrate that an inducible 86 kd nuclear protein termed HIVENIM specifically binds to both the enhancer element of the HIV-1 LTR and a closely related 12 bp sequence present in the 5’regulatory region (-267 to-256) of the IL-2Ra gene. The interaction of these binding sites with HIVEN86A and perhaps other cellular proteins such as NF-KB appears importantly involved in mitogen activation since the isolated IL-2Ra promoter binding site or single elements of the normally duplicated HIV-1 enhancer alone are sufficient to confer mitogen inducibility on an unresponsive heterologous promoter. Together these findings suggest that the normal action of an inducible nuclear DNA binding protein (s) involved in the regulation of IL-2Ra gene expression can be subverted by the HIV-1 rovirus to promote activation of retroviral gene transcription. introduction

The growth of human T lymphocytes is dependent on mitogen-or antigen-induced expression of the cellular genes encoding interleukin-2 (IL-2) and IL-2 receptors (IL-2Rs)(Greene et al., 1986; Taniguchi et al., 1986). The binding of IL-2 to its high-affinity receptor transduces intracellular signals leading to T cell proliferation (Robb et al.,! 981, 1984). The high-affinity IL-2 receptor is now believed to be composed of two distinct IL-2 binding subunits: the Tat antigen (~ 55, IL-2Ra chain)(Leonard et al., 1982, 1984, 1985) and a recently recognized 70-75 kd polypeptide (~ 70, IL-2Rf3 chain)(Sharon et al., 1986; Tsudo et al., 1986; Teshigawara et al., 1987; Robb et al., 1987; Dukovich et al., 1987). Induction of IL-2Ra gene expression appears to play a key role in the transient display of high-affinity IL-2Rs at the cell surface since unstimulated T cells lack this gene product but constitutively express small amounts of the IL-2R8 (~ 70) protein (Le thi Bich Thuy et al., 1987).