Modulatory effects of the CCR5 antagonist maraviroc on microglial pro-inflammatory activation elicited by gp120

J Neurochem. 2012 Jan;120(1):106-14. doi: 10.1111/j.1471-4159.2011.07549.x. Epub 2011 Nov 17.


Despite important clinical benefits of the highly active antiretroviral therapy, neurological disorders affect approximately 50% of AIDS patients. In the brain, infected microglia release pro-inflammatory mediators as well as human immunodeficiency virus type 1 (HIV-1) proteins, like the envelope protein gp120, that sustain inflammation and mediate neuronal damage. Gp120 allows the virus entry in the host cells via binding to the CD4 receptor together with a specific co-receptor (CCR5/CXCR4). The antiretroviral drug maraviroc is a CCR5 receptor antagonist, approved for the treatment of HIV-experienced patients. By interfering with a chemokine receptor, highly expressed in microglia, maraviroc has the potential to modulate their activation during HIV-1 infection. To test this hypothesis, primary cultures of rat cortical microglia were activated by gp120. Gp120(CN54) , a protein derived by macrophage (M)-tropic viruses, showed strong pro-inflammatory action, thus it was used to test the effects of maraviroc. The latter displayed opposite effects, depending on whether or not interferon-γ (IFNγ) was also present in the system. IFNγ significantly enhanced gp120 proinflammatory activity, possibly via up-regulation of CCR5 receptor expression. In this experimental paradigm, maraviroc significantly increased microglial activation, thus suggesting that its chronic use can exacerbate neuronal pathology, especially in HIV-experienced patients with higher cerebral IFNγ levels.

MeSH terms

  • Animals
  • Blotting, Western
  • CCR5 Receptor Antagonists*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cyclohexanes / pharmacology*
  • Cyclohexanes / toxicity
  • Cytokines / biosynthesis
  • DNA Primers
  • Dinoprostone / metabolism
  • HIV Envelope Protein gp120 / antagonists & inhibitors*
  • HIV Envelope Protein gp120 / pharmacology*
  • HIV Infections / pathology
  • Inflammation / pathology*
  • Interferon-gamma / pharmacology
  • Macrophage Activation / drug effects*
  • Maraviroc
  • Microglia / drug effects*
  • Nitric Oxide / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Triazoles / pharmacology*
  • Triazoles / toxicity


  • CCR5 Receptor Antagonists
  • Cyclohexanes
  • Cytokines
  • DNA Primers
  • HIV Envelope Protein gp120
  • RNA, Messenger
  • Triazoles
  • Nitric Oxide
  • Interferon-gamma
  • Dinoprostone
  • Maraviroc