Human immunodeficiency virus type 1 clade B and C gp120 differentially induce neurotoxin arachidonic acid in human astrocytes: implications for neuroAIDS

J Neurovirol. 2011 Jun;17(3):230-8. doi: 10.1007/s13365-011-0026-5. Epub 2011 Apr 14.


HIV-1 clades (subtypes) differentially contribute to the neuropathogenesis of HIV-associated dementia (HAD) in neuroAIDS. HIV-1 envelop protein, gp120, plays a major role in neuronal function. It is not well understood how these HIV-1 clades exert these neuropathogenic differences. The N-methyl-D: -aspartate (NMDA) receptor-reduced glutamine synthesis could lead to secretion of neurotoxins such as arachidonic acid (AA) which plays a significant role in the neuropathogenic mechanisms in neuroAIDS. We hypothesize that clade B and C gp120 proteins exert differential effects on human primary astrocytes by production of the neurotoxin arachidonic acid. Our results indicate that clade B gp120 significantly downregulated NMDA receptor gene and protein expression, and level of glutamine while increasing expression of prostaglandin E2 (PGE(2)) and thromboxane A2 receptor (TBXA(2) R) compared to HIV-1 clade C gp120 protein. Thus, our studies for the first time demonstrate that HIV-1 clade B-gp120 protein appears to induce higher levels of expression of the neuropathogenic molecule cyclooxygenase-2 (COX-2)-mediated arachidonic acid by-products, PGE(2), and TBXA(2) R compared to HIV-1 clade C gp120 protein. These studies suggest that HIV-1 clade B and C gp120 proteins may play a differential role in the neuropathogenesis of HAD in neuroAIDS.

Publication types

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

MeSH terms

  • AIDS Dementia Complex / metabolism*
  • AIDS Dementia Complex / pathology
  • Arachidonic Acid / biosynthesis*
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Astrocytes / virology
  • Cell Culture Techniques
  • Cells, Cultured
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / biosynthesis
  • Down-Regulation
  • Glutamine / biosynthesis
  • HIV Envelope Protein gp120 / metabolism
  • HIV Envelope Protein gp120 / pharmacology*
  • HIV Infections / metabolism*
  • HIV Infections / pathology
  • HIV-1 / physiology
  • Humans
  • Neurotoxins / biosynthesis*
  • Protein Isoforms / metabolism
  • Protein Isoforms / pharmacology*
  • Receptors, N-Methyl-D-Aspartate / biosynthesis
  • Receptors, Thromboxane A2, Prostaglandin H2 / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation


  • HIV Envelope Protein gp120
  • Neurotoxins
  • Protein Isoforms
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Glutamine
  • Arachidonic Acid
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Dinoprostone