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lüll HIV regulation of the IL-7R: a viral mechanism for enhancing HIV-1 replication in human macrophages in vitro Zhang M; Drenkow J; Lankford CS; Frucht DM; Rabin RL; Gingeras TR; Venkateshan C; Schwartzkopff F; Clouse KA; Dayton AIJ Leukoc Biol 2006[Jun]; 79 (6): 1328-38We report a novel mechanism, involving up-regulation of the interleukin (IL)-7 cytokine receptor, by which human immunodeficiency virus (HIV) enhances its own production in monocyte-derived macrophages (MDM) in vitro. HIV-1 infection or treatment of MDM cultures with exogenous HIV-1 Tat(86) protein up-regulates the IL-7 receptor (IL-7R) alpha-chain at the levels of steady-state RNA, protein, and functional IL-7R on the cell surface (as measured by ligand-induced receptor signaling). This IL-7R up-regulation is associated with increased amounts of HIV-1 virions in the supernatants of infected MDM cultures treated with exogenous IL-7 cytokine. The overall effect of IL-7 stimulation on HIV replication in MDM culture supernatants is typically in the range of one log and greater. The results are consistent with a model in which HIV infection produces the Tat protein, which in turn up-regulates IL-7R in a paracrine manner. This results in increased IL-7R signaling in response to the IL-7 cytokine, which ultimately promotes early events in HIV replication, including binding/entry and possibly other steps prior to reverse transcription. The results suggest that the effects of IL-7 on HIV replication in MDM should be considered when analyzing and designing clinical trials involving treatment of patients with IL-7 or Tat vaccines.|*Models, Biological[MESH]|Cells, Cultured/drug effects/metabolism/virology[MESH]|Gene Products, tat/*physiology[MESH]|Genes, tat[MESH]|HIV Reverse Transcriptase/metabolism[MESH]|HIV-1/*physiology[MESH]|Humans[MESH]|Interleukin-7/adverse effects/pharmacology/*physiology[MESH]|Macrophages/drug effects/metabolism/*virology[MESH]|Paracrine Communication[MESH]|STAT3 Transcription Factor/metabolism[MESH]|Virion[MESH]|Virus Replication/drug effects/*physiology[MESH]|tat Gene Products, Human Immunodeficiency Virus[MESH] |