CRITICAL INVOLVEMENT OF HUMAN T-CELL LEUKEMIA VIRUS TYPE 1 TAX PROTEIN IN IL-2-INDEPENDENT TRANSFORMATION OF T-CELLS

Abstract

O-13 Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia. Tax, the viral protein, is thought to be crucial in the development of the disease, since it is transforming in vitro and induces tumors in transgenic animals. We examined the effect of Tax activity on the growth of an interleukin (IL)-2-dependent T-cell line, CTLL-2. A stable expression of Tax in CTLL-2 converted cell growth from being IL-2-dependent to IL-2-independent. Tax stimulated the transcription through NF-κB and cAMP responsive element like sequence (CRE) in HTLV-1 promoter. Tax mutants segregating these two pathways suggested that the NF-κB pathway was essential for IL-2-independent growth of CTLL-2, while that of CRE was unnecessary. However, both pathways were necessary for another transformation-related activity (colony formation in soft agar) of CTLL-2/Tax. Our results show that Tax has at least two distinct activities on T-cells, and suggest that Tax plays a crucial role in IL-2-independent T-cell transformation induced by HTLV-1 in addition to its well known IL-2-dependent cell transformation.