Estradiol negatively regulates HIV-LTR promoter activity in glial cells

Melinda E. Wilson, Kimberly F. Allred, Anthony J. Bisotti, Annadora Bruce-Keller, Ashok Chuahan, Avindra Nath

Research output: Contribution to journalArticlepeer-review

Abstract

HIV-associated dementia results from neuronal loss and an alteration of neuronal function due to a loss of synapses. While HIV infection in astrocytes is limited, astrocytes exhibit a chronic nonproductive infection that can lead to the release of neurotoxic proteins. Additionally, infection can disrupt the normal neurotrophic role of astrocytes that results in neuronal death. Gonadal steroid hormones are known to act as trophic and protective factors in the brain under a variety of normal and pathological conditions. In the present study, to determine if estrogen plays a role in the ability of Tat to function as a transcriptional activator within astrocytes, we examined the effect of estrogen on regulation of viral transcription. We utilized an immortalized human astrocyte cell line (SVGA) stably transfected with a reporter plasmid containing the HIV-1HIB LTR driving the chloramphenicol acetyltransferase (CAT) gene. The amount of transcriptional activity was measured by quantifying the amount of CAT produced. We determined that 17β-estradiol treatment (1 nM) had no effect on basal LTR activity. Following transfection with a Tat-expressing plasmid, there was a 100-fold increase in CAT production. This induction was reduced by 40% in cells pretreated with 17β-estradiol. 17β-Estradiol only suppressed transcription stimulated by Tat. Furthermore, we determined that this effect was specific to 17β-estradiol and estrogen receptor agonists. This activity was limited to astrocytes as no effect was observed in a monocytic cell line. Finally, the mechanism of action did not involve an alteration in levels of Cdk9 or Cyclin T1 proteins necessary for Tat activation of the HIV-1 LTR. This study demonstrates a novel activity of 17β-estradiol in glial cells that could play a role in the maintenance of neuronal health during HIV infection of the central nervous system.

Original languageEnglish (US)
Pages (from-to)350-356
Number of pages7
JournalAIDS research and human retroviruses
Volume22
Issue number4
DOIs
StatePublished - Apr 2006

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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