Extracellular HIV-1 Tat protein up-regulates the expression of surface CXC-chemokine receptor 4 in resting CD4(+) T cells

Here we report that synthetic HIV-1 Tat protein, immobilized on a solid sub strate, up-regulates the surface expression of the CXC-chemokine receptor 4 (CXCR4), but not of the CC-chemokine receptor 5 in purified populations of primary resting CD4(+) T cells. The Tat-mediated increase of CXCR4 occurre d in a well-defined range of concentrations (1-10 nM of immobilized Tat) an d time period (4-8 h postincubation). Moreover, the increase of CXCR4 was a ccompanied by an increased entry of the HXB2 T cell line-tropic (X4-tropic) , but not of the BaL macrophage-tropic strain of HIV-1. The ability of Tat to up-regulate CXCR4 expression was abrogated by the protein synthesis inhi bitor cycloheximide, clearly indicating the requirement of de novo synthesi s. As Tat protein is actively released by HIV-1 infected cells, our data in dicate a potentially important role for extracellular Tat in rendering byst ander CD4(+) T cells more susceptible to infection with X4-tropic HIV-1 iso lates.