HIV regulation of the IL-7R: A viral mechanism for enhancing HIV-1 replication in human macrophages in vitro

Zhang, M., Drenkow, J., Lankford, C. S. R., Frucht, D. M., Rabin, R. L., Gingeras, T. R., Venkateshan, C., Schwartzkopff, F., Clouse, K. A., Dayton, A. I. (2006) HIV regulation of the IL-7R: A viral mechanism for enhancing HIV-1 replication in human macrophages in vitro. Journal of Leukocyte Biology, 79 (6). pp. 1328-1338. ISSN 07415400 (ISSN)

DOI: 10.1189/jlb.0704424


We 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) α-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.

Item Type: Paper
Uncontrolled Keywords: AIDS Cytokine receptors Cytokines Tat interleukin 7 interleukin 7 receptor interleukin 7alpha receptor protein tat 86 RNA transactivator protein virus protein RNA directed DNA polymerase STAT3 protein STAT3 protein human article controlled study human human cell Human immunodeficiency virus 1 Human immunodeficiency virus infection in vitro study macrophage function priority journal receptor upregulation signal transduction steady state virion virus replication virus transmission biological model cell culture drug effect macrophage metabolism paracrine signaling physiology regulator gene virology Human immunodeficiency virus Cells Cultured Gene Products tat Genes, tat HIV-1 HIV-1 Reverse Transcriptase Humans Interleukin-7 Macrophages Models Biological Paracrine Communication STAT3 Transcription Factor
Subjects: diseases & disorders > viral diseases > HIV
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein receptor
CSHL Authors:
Communities: CSHL labs > Gingeras lab
Depositing User: CSHL Librarian
Date: 2006
Date Deposited: 08 Mar 2012 17:23
Last Modified: 15 Jul 2013 13:29
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