Immunoneuropathogenesis of HIV-1 clades B and C: role of redox expression and thiol modification

Free Radic Biol Med. 2014 Apr;69:136-44. doi: 10.1016/j.freeradbiomed.2013.12.025. Epub 2014 Jan 27.

Abstract

Previous studies have shown that, during infection, HIV-1 clade B and clade C differentially contribute to the neuropathogenesis and development of HIV-associated neurocognitive disorders (HANDs). The low-molecular-weight tripeptide glutathione (GSH) alters the redox balance and leads to the generation of reactive oxygen species, which play a significant role in the neuropathogenesis of HANDs. We hypothesized that the HIV-1 clade B and clade C viruses and their respective Tat proteins exert differential effects on monocyte-derived immature dendritic cells (IDCs) and neuroblastoma cells (SK-N-MC) by redox activation, which leads to immunoneuropathogenesis. The GSH/GSSG ratio and mRNA expression levels and protein modification of glutathione synthetase (GSS), glutathione peroxidase 1 (GPx1), superoxide dismutase 1 (SOD1), and catalase (CAT) were analyzed in IDCs infected with HIV-1 clade B or clade C as well as in cells treated with the respective Tat proteins. The results indicated that HIV-1 clade B virus and its Tat protein significantly increased the production of reactive oxygen species and reduced the GSH/GSSG ratio and subsequent downregulation of gene expression and protein modification of GSS, GPx1, SOD1, and CAT compared to infection with the clade C virus or treatment with the clade C Tat protein. Thus, our studies demonstrate that HIV-1 clades B and C exert differential effects of redox expression and thiol modification. HIV-1 clade B potentially induces oxidative stress, leading to more immunoneuropathogenesis than infection with HIV-1 clade C.

Keywords: Dendritic cells; Free radicals; Glutathione; HIV-1 clade B; HIV-1 clade C; Neuron; Oxidative stress.

Publication types

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

MeSH terms

  • AIDS Dementia Complex / metabolism
  • AIDS Dementia Complex / pathology
  • AIDS Dementia Complex / virology*
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Dendritic Cells / pathology
  • Glutathione / metabolism
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • HIV-1 / pathogenicity
  • Humans
  • Oxidation-Reduction*
  • Reactive Oxygen Species / metabolism
  • Sulfhydryl Compounds / administration & dosage
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase-1

Substances

  • Reactive Oxygen Species
  • SOD1 protein, human
  • Sulfhydryl Compounds
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Glutathione