Activation of Egr-1 expression in astrocytes by HIV-1 Tat: new insights into astrocyte-mediated Tat neurotoxicity

J Neuroimmune Pharmacol. 2011 Mar;6(1):121-9. doi: 10.1007/s11481-010-9217-8. Epub 2010 Apr 23.


Human immunodeficiency virus type 1 (HIV-1) Tat plays an important role in HIV-associated neuropathogenesis; the underlying mechanisms are still evolving. We have recently shown that HIV-1 Tat induces expression of glial fibrillary acidic protein (GFAP), a characteristic of HIV-1 infection of the central nervous system. We have also shown that the Tat-induced GFAP expression in astrocytes is regulated by p300 and that deletion of the early growth response 1 (Egr-1) cis-transacting element within the p300 promoter abolishes Tat-induced GFAP expression. In this study, we further examined the relationship between Tat and Egr-1 in astrocytes. We found increased Egr-1 protein expression in Tat-expressing human astrocytoma cells and mouse primary astrocytes. Using the Egr-1 promoter-driven firefly luciferase reporter gene assay and the site-directed mutagenesis, we demonstrated that Tat increased Egr-1 expression by transactivating the Egr-1 promoter and involving specific serum response elements within the promoter. Consistent with these data, we showed that Tat transactivation of the Egr-1 promoter was abrogated when astrocytes were cultured in serum-reduced media. Taken together, these results reveal that Tat directly transactivates Egr-1 expression and suggest that Tat interaction with Egr-1 is probably one of the very upstream molecular events that initiate Tat-induced astrocyte dysfunction and subsequent Tat neurotoxicity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Astrocytes / pathology
  • Astrocytes / virology*
  • Blotting, Western
  • Cell Line
  • Cells, Cultured
  • Early Growth Response Protein 1 / biosynthesis*
  • Early Growth Response Protein 1 / genetics
  • Gene Expression
  • HIV Infections / genetics
  • HIV Infections / metabolism
  • HIV-1 / metabolism
  • Humans
  • Mice
  • Mice, Transgenic
  • Promoter Regions, Genetic / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptional Activation / genetics*
  • Transfection
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*


  • EGR1 protein, human
  • Early Growth Response Protein 1
  • tat Gene Products, Human Immunodeficiency Virus