HIV-1 tat induces the expression of a new hematopoietic cell-specific transcription factor and downregulates MIP-1...

MIP-1 alpha is a secreted chemokine which can inhibit hematopoietic stem 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. It is also expressed in transformed B-cells. We have previously identified a new transcription factor family (the MNP family) whose expression is crucial for the induction of MIP-1 alpha transcription during cellular activation and in transformed B cells. Monocytes and transformed B-cells normally express MNP-1 strongly and MNP-2 weakly, while T-cells strongly express only MNP-2. Recently, we reported that HIV-1 tat downregulates 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. Expression of neither HTLV-1 tax in Jurkat T-cells nor EBV in B-cells had any effect on MNP-1 or MNP-2 expression, showing that the effect is specific for HIV-1 tat. We propose that HIV-1 tat may inhibit MIP-1 alpha expression by inducing MNP-1 expression in T-cells, probably by either competing with MNP-2 for binding to the MIP-1 alpha promoter or by sequestering it into inactive forms.