The effect of HIV-1 regulatory proteins on cellular genes: derepression of the IL-2 promoter by Tat
In HIV-infected individuals dysregulation of the immune system is characterized by severe disorders of the cytokine network. Increase secretion of IL-2, the major T cell growth and differentiation cytokine, may play a decisive role in sensitization of T cells for activation induced apoptosis and ind...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
16 May 2001
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| In: |
European journal of immunology
Year: 2001, Volume: 31, Issue: 6, Pages: 1790-1799 |
| ISSN: | 1521-4141 |
| DOI: | https://doi.org/10.1002/1521-4141(200106)31:6<1790::AID-IMMU1790>3.0.CO;2-G |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/https://doi.org/10.1002/1521-4141(200106)31:6<1790::AID-IMMU1790>3.0.CO;2-G Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/1521-4141%28200106%2931%3A6%3C1790%3A%3AAID-IMMU1790%3E3.0.CO%3B2-G 
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| Author Notes: | Andreas Ehret, Min Li‐Weber, Rainer Frank and Peter H. Krammer |
| Summary: | In HIV-infected individuals dysregulation of the immune system is characterized by severe disorders of the cytokine network. Increase secretion of IL-2, the major T cell growth and differentiation cytokine, may play a decisive role in sensitization of T cells for activation induced apoptosis and indirect death of activated T cells through augmented virus replication. We investigated the cause of enhanced IL-2 secretion and found that the HIV Tat induces this effect. We demonstrate that increased IL-2 secretion is due to Tat-enhanced IL-2 promoter activation. Tat derepresses and activates the distal AP-1 site (position -185 to -177) in the IL-2 promoter. In nonstimulated T cells a repressor complex containing NF-IL6, JunB, c-Fos and Fra-1 is formed on the AP-1IL-2/d site and represses IL-2 promoter activity. After T cell activation, a heterodimeric activator containing p65 and c-Jun binds to the AP-1IL-2/d site. HIV Tat enhances activation of NF-κB and consequently, activates the AP-1IL-2/d site. Our data provide evidence for a novel mechanism by which HIV Tat dysregulates IL-2 production and therefore may contribute to the HIV-1 infection in a way yet to be clarified. |
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| Item Description: | Gesehen am 28.04.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1521-4141 |
| DOI: | https://doi.org/10.1002/1521-4141(200106)31:6<1790::AID-IMMU1790>3.0.CO;2-G |