Metabolic profiling during HIV-1 and HIV-2 infection of primary human monocyte-derived macrophages

Virology. 2016 Apr:491:106-14. doi: 10.1016/j.virol.2016.01.023. Epub 2016 Feb 16.

Abstract

We evaluated cellular metabolism profiles of HIV-1 and HIV-2 infected primary human monocyte-derived macrophages (MDMs). First, HIV-2 GL-AN displays faster production kinetics and greater amounts of virus as compared to HIV-1s: YU-2, 89.6 and JR-CSF. Second, quantitative LC-MS/MS metabolomics analysis demonstrates very similar metabolic profiles in glycolysis and TCA cycle metabolic intermediates between HIV-1 and HIV-2 infected macrophages, with a few notable exceptions. The most striking metabolic change in MDMs infected with HIV-2 relative to HIV-1-infected MDMs was the increased levels of quinolinate, a metabolite in the tryptophan catabolism pathway that has been linked to HIV/AIDS pathogenesis. Third, both HIV-1 and HIV-2 infected MDMs showed elevated levels of ribose-5-phosphate, a key metabolic component in nucleotide biosynthesis. Finally, HIV-2 infected MDMs display increased dNTP concentrations as predicted by Vpx-mediated SAMHD1 degradation. Collectively, these data show differential metabolic changes during HIV-1 and HIV-2 infection of macrophages.

Keywords: Glycolysis; HIV-1; HIV-2; LC–MS/MS; Macrophages; Metabolites; TCA.

Publication types

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

MeSH terms

  • Cells, Cultured
  • Citric Acid Cycle
  • Glycolysis
  • HIV Infections / genetics
  • HIV Infections / metabolism*
  • HIV Infections / virology*
  • HIV-1 / physiology*
  • HIV-2 / physiology*
  • Humans
  • Macrophages / metabolism*
  • Macrophages / virology
  • Metabolome*
  • Monocytes / metabolism*
  • Monocytes / virology