HIV-1 tat induces the expression of a new hematopoietic cell-specific transcription factor and downregulates MIP-1 alpha gene expression in activated T-cells.
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.
Sharma
V
V
Department of Biology, University of West Florida, Pensacola 32514, USA.
Xu
M
M
Ritter
L M
LM
Wilkie
N M
NM
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D001483:Base Sequence; D001773:Blood Cells; D002460:Cell Line; D002461:Cell Line, Transformed; D054407:Chemokine CCL4; D017931:DNA Primers; D015967:Gene Expression Regulation, Viral; D015756:Genes, tat; D006131:Growth Inhibitors / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D015846:Monokines / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014157:Transcription Factors / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D054407:Chemokine CCL4; D017931:DNA Primers; D006131:Growth Inhibitors; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D014157:Transcription Factors