HIV-1 TAT INDUCES THE EXPRESSION OF A NEW HEMATOPOIETIC CELL-SPECIFICTRANSCRIPTION FACTOR AND DOWN-REGULATES MIP-1-ALPHA GENE-EXPRESSION IN ACTIVATED T-CELLS

MIP-1 alpha is a secreted chemokine which can inhibit hematopoietic st em cells and modulate inflammatory responses. It is also an inhibitor of HIV replication in CD8(+) T-cells. The expression of MIP-1 alpha is induced during cellular activation of CD4(+) T-cells and monocytes. I t is also expressed in transformed B-cells. We have previously identif ied a new transcription factor family (the MNP family) whose expressio n is crucial for the induction of MIP-1 alpha transcription during cel lular activation and in transformed B cells. Monocytes and transformed B-cells normally express MNP-1 strongly and MNP-2 weakly, while T-cel ls strongly express only MNP-2. Recently. we reported that HIV-1 rat d ownregulates MIP-1 alpha expression in Jurkat T-cells. In this report we show induction of MNP-1 in Jurkat T-cells expressing HIV-1 tat. Exp ression of neither HTLV-1 tar in Jurkat T-cells nor EBV in B-cells had any effect on MNP-1 or MNP-2 expression, showing that the effect is s pecific for HIV-1 tat. We propose that HIV-1 rat may inhibit MIP-1 alp ha expression by inducing MNP-1 expression in T-cells, probably by eit her competing with MNP-2 for binding to the MIP-1 alpha promoter or by sequestering it into inactive forms. (C) 1996 Academic Press, Inc.