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  • Title: Interferon downregulates CXCR4 (fusin) gene expression in peripheral blood mononuclear cells.
    Author: Shirazi Y, Pitha PM.
    Journal: J Hum Virol; 1998; 1(2):69-76. PubMed ID: 10195234.
    Abstract:
    OBJECTIVE: Cytokines modulate human immunodeficiency virus type 1 (HIV-1) replication at multiple stages of its life cycle. We examined the effects of several HIV-1-stimulatory and HIV-1-inhibitory cytokines on CXCR4 (fusin) gene expression in lymphoid cells. STUDY DESIGN/METHODS: Peripheral blood mononuclear cells (PBMCs) were treated with various cytokines, and CXCR4 gene expression was assessed by Northern blot analysis. Cell-cell fusion was assessed using HeLa-MAGI cells expressing T-cell-tropic HIV-1 (i.e., LAV strain) envelope glycoproteins and U937 cells expressing HIV-1 tat. RESULTS: Although treatment of PBMCs with interferon-alpha (IFN-alpha) and IFN-gamma led to a significant repression of CXCR4 gene expression, interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) had no significant effect on CXCR4 gene expression in PBMCs. IFN-alpha and IFN-gamma also inhibited CXCR4 gene expression in the promyelocytic cell line U937, and this inhibition led to a decrease in cell-cell fusion between U937 cells and HeLa-MAGI cells. In U937 cells, TNF-alpha and phorbol myristate acetate (PMA) stimulated CXCR4 gene transcription; this effect was reversed with prior treatment of cells with IFN-gamma. CONCLUSIONS: IFN-alpha and IFN-gamma effectively downmodulate fusin gene expression in lymphoid cells, indicating that IFNs modulate HIV-1 replication at postentry levels as well as at the level of HIV-1 entry.
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