The Human T-cell leukemia virus type 1 (HTLV-1) non-structural protein Tax plays a crucial role incellular transformation. It activates the transcription factors of various cellular genes and interacts with cellular proteins. There is limited data available on the interaction between specific T-cell transcription factor GATA3 and Tax. Implications for the significance of GATA3 in T-cell development and function, T helper2 (Th2) differentiation, and a role of GATA3 during the immune response have been reported. To determine the effect of the Tax protein on GATA3 gene expression, we investigated the interaction between this protein and the GATA3 promoter and repressor regions. Results demonstrated an interaction between Tax and the GATA3promoter via the transcription factor Sp1 and a role for Tax in the negative regulation of GATA3 expression, through its interaction with the repressor ZEB. This interaction may be involved in the pathophysiology of adult T-cell leukemia/lymphoma (ATL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). (C) 2004 Wiley-Liss, Inc.93611781187