Investigation of Neuropathogenesis in HIV-1 Clade B and C Infection Associated with IL-33 and ST2 Regulation

ACS Chem Neurosci. 2015 Sep 16;6(9):1600-12. doi: 10.1021/acschemneuro.5b00156. Epub 2015 Jul 15.


In present research work, for the first time, we demonstrate that neuropathogenesis in HIV-1 clade B and C infection is associated with IL-33 and ST2 dysregulation, that is, implication toward neuropathogenesis. It is known that neuropathogenesis of HIV infected individuals is clade dependent. Proinflammatory cytokines and related receptors play a significant role in the complex regulatory mechanisms of neuropathogenesis in HIV-1 infection. Among them, IL-33 is an inflammatory cytokine expressed in the central nervous system (CNS) and activates microglia cells and may affect neuroimmune inflammatory processes involved in HIV neuropathogenesis. Beside this, IL-33 receptor (ST2) plays a role in neuroinflammatory processes through the modulation of the biological action of IL-33. quantitative real time PCR (qRT-PCR), ELISA, Western blot (WB), and flow cytometry experiments were performed to elucidate the role of IL-33/ST2 in HIV neuropathogenesis in CNS cells. Apoptosis and mechanisms of IL-33 in neuronal cells were studied using caspase-3 assay and RT-PCR. Results of the studies suggest that the infection in CNS cells with HIV-1 clade B resulted in higher levels of IL-33/ST2L expression compared to HIV-1 clade C infection. Furthermore, higher concentrations of IL-33 were associated with a decrease in myocyte enhancer factor 2C (MEF2C) expression, a transcription factor that regulates synaptic function, and an increase in apoptosis, NOD2, and SLC11A1 in clade B infection. This led to neuroinflammation which dysregulates synaptic function and apoptosis. These parameters are common in neuroAIDS provoked by HIV infection.

Keywords: HIV-1; IL-33; Neuroinflammation; ST2; clade B; clade C; neuroAIDS; synaptic plasticity.

Publication types

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

MeSH terms

  • Apoptosis / physiology
  • Astrocytes / physiology
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cells, Cultured
  • Central Nervous System / physiopathology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • HIV Infections / physiopathology*
  • HIV-1* / classification
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33 / administration & dosage
  • Interleukin-33 / metabolism*
  • MEF2 Transcription Factors / metabolism
  • Neuroimmunomodulation / physiology
  • Neuronal Plasticity / physiology
  • Neurons / physiology*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cell Surface / metabolism*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / metabolism
  • Up-Regulation


  • IL1RL1 protein, human
  • IL33 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • MEF2 Transcription Factors
  • MEF2C protein, human
  • Receptors, Cell Surface
  • Recombinant Proteins
  • CASP3 protein, human
  • Caspase 3