The transcription factor GATA-1 potently represses the expression of the HIV-1 co-receptor CCR5 in human T cells and dendritic cells

Authors:
Sundrud MS, Vancompernolle SE, Eger KA, Bruno TC, Subramaniam A, Mummidi S, Ahuja SK and Unutmaz D
In:
Source: Blood
Publication Date: (2005)
Issue: 106(10): 3440-3448
Research Area:
Immunotherapy / Hematology
Cells used in publication:
T cell, human peripheral blood unstim.
Species: human
Tissue Origin: blood
T cell, human stim.
Species: human
Tissue Origin: blood
Dendritic cell (NHDC), human
Species: human
Tissue Origin: blood
CD34+ cell, human
Species: human
Tissue Origin: blood
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
CCR5 is the major HIV-1 co-receptor and its expression levels are a critical determinant of HIV-1 infection. However, the molecular mechanisms of CCR5 regulation in primary targets of HIV-1 remain unknown. Despite binding to conserved DNA-elements, we show that the transcription factors GATA-1 and GATA-3 differentially suppress the expression of CCR5 in stem cell-derived dendritic cells and primary human T cell subsets. In addition, GATA-1 expression was also more potent than GATA-3 in suppressing Th1 associated genes, IFNgamma and CXCR3. GATA-1, but not GATA-3, potently suppressed CCR5 transcription, thereby rendering human T cells resistant to CCR5-tropic HIV-1 infection. However, GATA-1 also substituted for GATA-3 in its canonical role of programming Th2 gene expression. These findings provide insight into GATA-3-mediated gene regulation during T cell differentiation. Importantly, decoding the mechanisms of GATA-1-mediated repression of CCR5 may offer an opportunity to develop novel approaches to inhibit CCR5 expression in T cells.