Abstract
BackgroundCXC chemokine receptor 4 (CXCR4), a member of the G-protein-coupled chemokine receptor family, can serve as a co-receptor along with CD4 for entry into the cell of T-cell tropic X4 human immunodeficiency virus type 1 (HIV-1) strains. Productive infection of T-lymphoblastoid cells by X4 HIV-1 markedly reduces cell-surface expression of CD4, but whether or not the co-receptor CXCR4 is down-regulated has not been conclusively determined.ResultsInfection of human T-lymphoblastoid cell line RH9 with HIV-1 resulted in down-regulation of cell surface CXCR4 expression. Down-regulation of surface CXCR4 correlated temporally with the increase in HIV-1 protein expression. CXCR4 was concentrated in intracellular compartments in H9 cells after HIV-1 infection. Immunofluorescence microscopy studies showed that CXCR4 and HIV-1 glycoproteins were co-localized in HIV infected cells. Inducible expression of HIV-1 envelope glycoproteins also resulted in down-regulation of CXCR4 from the cell surface.ConclusionThese results indicated that cell surface CXCR4 was reduced in HIV-1 infected cells, whereas expression of another membrane antigen, CD3, was unaffected. CXCR4 down-regulation may be due to intracellular sequestering of HIV glycoprotein/CXCR4 complexes.
Highlights
CXC chemokine receptor 4 (CXCR4), a member of the G-protein-coupled chemokine receptor family, can serve as a co-receptor along with CD4 for entry into the cell of Tcell tropic X4 human immunodeficiency virus type 1 (HIV-1) strains
HIV-1 infection down-regulates surface expression of CXCR4 in RH9 cells To determine whether HIV infection alters cell surface CXCR4 levels, RH9 T-lymphoblastoid cells were infected with HIV-1LA1 at a MOI of 4 or mock-infected
At 1, 4 and 7 days post infection (PI), the level of cell surface CXCR4 on RH9 cells and HIV-1-infected RH9 cells were determined by flow cytometric analysis using CXCR4 monoclonal antibody (MAb) 12G5 [39]
Summary
CXC chemokine receptor 4 (CXCR4), a member of the G-protein-coupled chemokine receptor family, can serve as a co-receptor along with CD4 for entry into the cell of Tcell tropic X4 human immunodeficiency virus type 1 (HIV-1) strains. Several members of the chemokine receptor family function as coreceptors with the primary receptor CD4 to allow entry of various strains of human immunodeficiency virus type. T-cell-tropic X4 HIV-1 use CD4 and chemokine receptor CXCR4 for entry into target cells, whereas macrophage-tropic R5 HIV-1 use CD4 and chemokine receptor CCR5. CCR3, CCR2, CXCR6 (Bonzo/STLR6) among other chemokine receptors can function as coreceptors and support infection by a more restricted subset of macrophage-tropic or dual-tropic HIV strains [9,10,5,11,12]
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